Hematology and Oncology Flashcards Preview

Step 1 boards > Hematology and Oncology > Flashcards

Flashcards in Hematology and Oncology Deck (262)
1

Erythrocyte

Carries O2 to tissues and CO2 to lungs. Anucleate and biconcave, with large surface area-to-volume ratio for rapid gas exchange. There lifespan is 120 days. Source of energy is glucose (90% used in glycolysis, 10% used in HMP shunt). Membrane contains Cl-/HCO3- antiporter, which allows RBCs to export HCO3- and transport CO2 from the periphery to the lungs for elimination. Eryth=red; cyte=cell.

2

Erythrocytosis

polycythemia; an increase hematocrit

3

Anisocytosis

varying sizes of RBCs

4

Poikilocytosis

varying shapes of RBCs.

5

Reticulocyte

an immature RBC; reflects erythroid proliferation.

6

Thrombocyte

Platelet. Involved in primary hemostasis. Small cytoplasmic fragment derived from megakaryocytes. Life span of 8-10 days. When activated by endothelial injury, aggregates with other platelets and interacts with fibrinogen to form platelets and interacts with fibrinogen to form platelet plug. Contains dense granules (ADP and Ca) and alpha granules (vWF and fibrinogen). Approximately 1/3 of platelet pool is stored in the spleen. Thrombocytopenia or a decrease in platelet function results in petechiae. vWF receptor binds GpIb. Fibrinogen receptor binds GpIIb/IIIa.

7

Leukocyte

Divided into granulocytes (neutrophil, eosinophil, basophil) and mononuclear cells (monocytes, lymphocytes). Responsible for defense against infections. Normally 4,000-10,000 cells/mm3.

8

WBC differential

Neutrophils: 54-62%. Lymphocytes: 25-33%. Monocytes: 3-7%. Eosinophils: 1-3%. Basophils: 0-0.75%.

9

Neutrophil

Acute inflammatory response cell. Increased in bacterial infections. Phagocytic. Multilobed nucleus. Specific granules contain SLP, collagenase, lysozyme, and lactoferrin. Azurophilic granules (lysosomes) contain proteinases, acid phosphatase, myeloperoxidase, and beta-glucuronidase. Hypersegmented polys (5 or more lobes) are seen in vitamin B12/ folate deficiency. An increase in band cells (immature neutrophils) reflect states of increased myeloid proliferation (bacterial infections, CML). Important neutrophil chemotactic agents: C5a, IL-8, LTB4, Kallikerin, platelet-activating factor.

10

Monocyte

Differentiates into macrophages in tissues. Large, kidney shaped nucleus. Extensive frosted glass cytoplasm. Mono=one (nucleus); cyte=cell.

11

Macrophage

Phagocytoses bacteria, cellular debris, and senescent RBCs. Long life is tissues. Macrophages differentiate from circulating blood monocytes. Activated by gamma-interferon. Can function as antigen-presenting cell vis MHC II. Important component of granuloma formation (eg TB, sarcoidosis). Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock.

12

Eosinophil

Defends against helminthic injections (major basic protein). Bilobate nucleus. Pack with large eosinophilic granules of uniform size. Highly phagocytic for antigen-antibody complexes. Produces histaminase and major basic protein (MBP, a helminthotoxin).

13

Causes of eosinophilia

Neoplasia, Asthma, Allergic processes, Chronic adrenal insufficiency, Parasites (invasive) NAACP.

14

Basophil

Mediates allergic reaction. Densely basophilic granules contain heparin (anticoagulant) and histamine (vasodilator). Leukotrienes synthesized and released on demand. Basophilic is when stained with basic stains. Basophilia is uncommon, but can be a sign of myeloproliferative disease, particularly CML.

15

Mast cell

Mediates allergic reactions in local tissues. Mast cells contain basophilic granules and originate from the same precursor as basophils but are not the same cell type. Can bind the Fc portion of IgE to membrane. IgE cross-links upon antigen binding, causing degranulation, which releases histamine, heparin, and eosinophil chemotactic factors. Involved in type I hypersensitivity reactions. Cromolyn sodium prevents mast cell degranulation (used for asthma prophylaxis).

16

Dendritic cell

Highly phagocytic APC. Functions as link between innate and adaptive immune systems. Expresses MHC class II Fc receptors on surface. Called Langerhans cell in the skin.

17

Lymphocyte

Refers to B cells, T cells, and NK cells. B cells and T cells mediate adaptive immunity. NK cells are part of the innate immune response. Round, densely staining nucleus with small amount of pale cytoplasm.

18

B cell

Part of the humoral immune response. Originates from stem cells in bone marrow and matures in marrow. Migrates to peripheral lymphoid tissue (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue). When antigen is encountered, B cells differentiate into plasma cells (which produce antibodies) and memory cells. Can functions as an APC via MHC II. They have CD19, CD21, CD20. B=Bone marrow

19

T cell

Mediates cellular immune response. Originates from stem cells in the bone marrow, but matures in the thymus. T cells differentiate into cytotoxic T cells (express CD8, recognize MHC I), helper T cells (express CD4, recognize MHC II), and regulatory T cells. CD28 (co-stimulatory signal) necessary for T-cell activation. The majority of circulating lymphocytes are T cells (80%). T is for Thymus. CD4+ helper T cells are the primary target of HIV. MHCxCD=8 (eg MHC 2 x CD4=8, and MHC 1 x CD8=8).

20

Plasma cell

Produces large amounts of antibody specific to a particular antigen. Clock-face chromatin distribution, abundant RER, and well-developed Golgi apparatus. Multiple myeloma is a plasma cell cancer.

21

Group A blood

Group A antigens on RBC surface. Antibodies are IgM anti-B. If a patient receive B or AB, they have a hemolytic reaction.

22

Group B blood

Group B antigens on RBC surface. Antibodies are IgM anti-A. If a patient receive A or AB, they have a hemolytic reaction.

23

Group AB blood

Group A and B antigens on RBC surface. There are no antibodies. They are universal recipients of RBCs. If a patient receive B or AB, they have a hemolytic reaction.

24

Group O blood

No group antigens. They are universal donor of RBCs. Antibodies are IgM anti-B and anti-A. If a patient receive any non O blood, they have a hemolytic reaction.

25

Rh positive blood

There are Rh (D) antigens and no anti-D antibody.

26

Rh negative blood

There are no Rh (D) antigens. There are IgG anti-D. Rh negative mothers need to be treated with Rh (D) immunoglobulin after each pregnancy to prevent anti-D IgG formation.

27

Hemolytic disease of the newborn

IgM does not cross the placenta but IgG does cross placenta. Rh negative mothers exposed to fetal Rh positive blood (often during delivery) may make anti-D IgG. In subsequent pregnancies, anti-D IgG crosses the placenta causes hemolytic disease of the newborn (erythroblastosis fetalis) in the next fetus that is Rh positive. Prevented by administration of RhoGAM to Rh negative pregnant women during the third trimester, which prevents maternal anti-Rh IgG production. Rh negative mothers have anti-D IgG only if previously exposed to Rh positive blood.

28

Intrinsic coagulation pathway

The intrinsic pathway begins with Factor XII (Hageman factor), which is activated by subendothelial collagen. Factor XII activates factor XI, which activates IX. Factor IX requires Ca and VIII. Factor IX also activates factor X, the beginning of the combined pathway.

29

Extrinsic coagulation pathway

The extrinsic pathway begins with Factor VII (requires Ca), which is activated by tissue factor (aka Factor III or thromboplastin). Factor VII also activates factor X, the beginning of the combined pathway.

30

Combined coagulation pathway

The intrinsic and extrinsic pathway converge with the activation of Factor X. The common pathways begins with Factor X, and ends with the formation of fibrin polymers. Factor X requires Ca and V as cofactors and activates prothrombin to thrombin, which cleaves fibrinogen to form fibrin.

31

Fibrinolysis

Fibrinolysis is the dissolution of a clot. The clot releases the enzyme plasminogen activator (tPA), which activates plasminogen to plasmin. Plasmin lyses fibrinogen and fibrin, dissolving the clot slowly. tPA is inhibited by aminocaproic acid. It is activated by alteplase, reteplase, steptokinase, and tenecteplase.

32

Anticoagulants that target factor X

Includes LMWH (greatest efficacy), heparin, direct Xa inhibitors (apixaban, rivaroxaban), fondaparinux.

33

Anticoagulants that target factor II (thrombin)

Includes heparin (greatest efficacy), LMWH (dalteparin, enoxaparin), direct thrombin inhibitors (argatroban, bivalirudin, dabigatran).

34

Kinin cascade

Kallikrein converts HMWK to bradykinin, which causes an increase in vasodilation, permeability, and pain. HMWK also activates XII, the first step of the intrinsic coagulation pathway.

35

Vitamin K as a procoagulation cascade components

Oxidized vitamin K get converted to reduced vitamin K by epoxide reductase. Vitamin K acts as a cofactor for factors II, VII, IX, X, C, S. Warfarin inhibits the enzyme vitamin K epoxide reductase. Neonates lack enteric bacteria, which produce vitamin K. A vitamin K deficiency decreases synthesis of factors II, VII, IX, C, protein C, and protein S. vWF carries/ protects VIII.

36

Protein C

Protein C is activated by thrombin-thrombomodulin complex from endothelial cells, which cleaves and inactivates V and VIII with protein S as a cofactor. Factor V Leiden mutation produces a factor V resistant to inhibition by activated protein C.

37

tPA

tPA converts plasminogen to plasmin, which causes fibrinolysis by cleaving the fibrin mesh and destruction of coagulation factors.

38

Antithrombin

It inhibits activated forms of factors II, VII, IX, X, XI, XII. Heparin enhances the activity of antithrombin. The principal targets of antithrombin include thrombin and factor X.

39

Platelet plug formation (primary hemostasis)

Endothelial damage leads to a transient vasoconstriction via neural stimulation reflex and endothelin (released from damaged cell). vWF binds to exposed collagen. vWF is from Weibel-Palade bodies of endothelial cells and alpha-granules of platelets. Platelets bind vWH via GP1b receptor at the site of injury only, causing platelets to undergo conformational change. Platelets release ADP and Ca (necessary for coagulation cascade) and TXA2 (a derivative of platelet cyclooxygenase. ADP helps platelet adhere to endothelium. ADP binds to a receptor, which induces GpIIb/GpIIIa expression at platelet surface. Fibrinogen binds GPIIb/GpIIIa receptors and links platelets. Temporary plug stops bleeding but it is unstable and can easily be dislodged.

40

Pro-platelet aggregation factors

TXA2 (released by platelets, aspirin inhibits cyclooxygenase), decreased blood flow, and increased platelet aggregation.

41

Anti- platelet aggregation factors

PGI2 and NO (released by endothelial cells), increased blood flow, decreased platelet aggregation.

42

Drugs that inhibit ADP-induced expression of GpIIb/GpIIIa

Clopidogrel, prasugrel, and ticlopidine

43

Drugs that inhibit GpIIb/GpIIIa directly

Abciximab, eptifibatide, and tirofiban

44

Drugs that activate vWF to bind GpIb

Ristocetin. Failure of agglutination with ristocetin assay occurs in von Willebrand disease and Bernard-Soulier syndrome.

45

Acanthocyte

A spur cell, a form of red blood cell that has a spiked cell membrane, due to abnormal thorny projections. It is associated with liver disease, abetalipoproteinemia. Acantho=spiny.

46

Basophilic stippling

Erythrocytes display small dots at the periphery. It is associated with lead poisoning.

47

Degamacyte

A bite cell. It is associated with G6PD deficiency

48

Elliptocyte

It is associated with hereditary elliptocytosis.

49

Macro-ovalocyte

An enlarged, oval-shaped erythrocytes (red blood cells). It is associated with megaloblastic anemia (also hypersegmented PMNs) and marrow failure.

50

Ringed sideroblast

An abnormal sideroblast with many iron granules in its mitochondria, found in a ring around the nucleus; seen in sideroblastic anemia.

51

Schistocyte

A helmet cell. It is associated with DIC, thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), HELLP syndrome (Hemolysis. Elevated Liver enzymes. Low Platelet count.), mechanical hemolysis (eg heart valve prosthesis).

52

Spherocyte

Sphere-shaped RBC, associated with hereditary spherocytosis, drug-and infection-induced hemolytic anemia.

53

Dacrocyte

Teardrop cell, associated with bone marrow infiltration (eg myelofibrosis). RBC sheds a tear because its mechanically squeezed out of its home in the bone marrow.

54

Target cell

It is associated HbC disease, Asplenia, Liver disease, and Thalassemia. (HALT, said the hunter to his target)

55

Heinz bodies

RBC with inclusions within red blood cells composed of denatured hemoglobin. Oxidation of Hb-SH groups to S-S causes Hb precipitation (Heinz body), with subsequent phagocytic damage to RBC membrane creating bite cells. It is associated with G6PD deficiency; Heinz body-like inclusions seen in alpha thalassemia.

56

Howell-Jolly bodies

Basophilic nuclear remnants found in RBCs. They are normally removed by splenic macrophages. They are seen in patients with functional hyposplenia or asplenia.

57

Microcytic anemia

Iron deficiency (late), anemia of chronic disease (late), thalassemias, lead poisoning, siderblastic anemia (late).

58

Nonhemolytic normocytic anemia

anemia of chronic disease, aplastic anemia, chronic kidney disease, iron deficiency (early).

59

Hemolytic normocytic anemia

Intrinsic causes include RBC membrane defect (hereditary spherocytosis), RBC enzyme deficiency (G6PD and pyruvate kinase), HbC defect, paroxysomal nocturnal hemoglobinuria, sickle cell anemia. Extrinsic causes include autoimmune, microangiopathic, macroangiopathic, and infections.

60

Megaloblastic macrocytic anemia

Folate deficiency, B12 deficiency, orotic aciduria

61

Non-megaloblastic macrocytic anemia

Liver disease, alcoholism, reticulocytosis.

62

Iron deficiency anemia

Microcytic, hypochromic anemia. A decrease in iron can occur due to chronic bleeding (eg GI loss, menorrhagia), malnurtion/absorption disorders, or an increase in demand (pregnancy), which causes there to be a decrease in the final step of heme synthesis. Findings include a decrease in iron, an increase in TIBC, a decrease in ferritin. Patients will have fatigue, conjunctival pallor, spoon nails (koilonychia). There will be microcytosis and hypochromia (central pallor). It may manifest as Plummer-Vinson syndrome.

63

Plummer-Vinson syndrome

It occurs due to iron deficiency anemia. It manifest as a triad of iron deficiency anemia, esophageal webs, and atrophic glossitis.

64

alpha-thalassemia

Microcytic, hypochromic anemia. The defect is a deletion of the alpha globin gene, which leads to a decrease in alpha globin synthesis. A cis deletion (αα/--) is prevalent in the Asian populations; trans deletion (α-/α-) prevalent in African populations. 1-2 allele deletion is less clinically severe anemia.

65

Hb Barts

4 alpha deletions. There is no alpha globin. Excess gamma-globin forms gamma four (Hb Barts). It is incompatible with life and leads to hydrops fetalis.

66

Hb H disease

This is 3 alpha deletion. There is very little alpha globin. Excess beta globin forms beta-4 (HbH).

67

Beta-thalassemia

Microcytic, hypochromic anemia. There are point mutations in the splice sites and promoter sequences, which leads to a decrease in beta-globin synthesis. There is high prevalence in mediterranean populations

68

Beta-thallassemia minor

Heterozygote in the beta gene. The beta chain is underproduced. It usually asymptomatic. It is diagnosed with an increase in HbA2 (above 3.5%) on electrophoresis.

69

Beta-thallassemia major

Homozygote in the beta gene. The beta chain is absent leading to severe anemia, requiring blood transfusions, which can lead to secondary hemochromatosis. On blood smear, there are anisocytosis, poikilocytosis, target cells, microcytosis, and schistocytes. Marrow expansion also occurs leading to skeletal deformities (crew cut on skull x-ray and chimunk facies). Extramedullary hematopoiesis, which leads to hepatosplenomegaly. This causes an increase risk of parvovirus B19-induced aplastic crisis. Major thallassemia also causes an increase in HbF (alpha2, gamma2). HbF is protective in the infant and disease becomes symptomatic only after 6 months.

70

Hb S/ Beta-thalassemia heterozygote

It causes mild to moderate sickle cell disease depending on amount of beta-globin production.

71

Lead poisoning anemia

Microcytic, hypochromic anemia. Lead inhibits the ferrochelatase and ALA dehydrogenase, leading to a decrease in heme synthesis and an increase in RBC protoporphyrin. It also inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA, causing basophilic stippling. There is high risk in old houses with chipped paint. LEAD: Lead Lines gingiva (burton lines) and on metaphyses of long bones on x-ray. Encephalopathy and Erythrocyte basophilic stippling. Abdominal colic and sideroblastic Anemia. Drops- wrist and foot drop. Dimercaprol and EDTA are 1st line of treatment. Succimer used for chelation for kids. (It SUCks to be kid who eats lead).

72

Sideroblastic anemia

Microcytic, hypochromic anemia. Due to a defect in heme synthesis. Inheritable causes include X-linked defect in delta-ALA synthase gene. Other causes include myelodysplastic syndromes (aquired) and reversible (alcohol is most common; also vitamin B6 deficiency, copper deficiency, isoniazid). Ringed sideroblasts (with iron-laden, Prussian blue-stained mitochondria) are seen in bone marrow. Other findings include an increase in iron, normal/ decrease in TIBC, increase in ferritin. Treatment includes pryidoxine (B6, cofactor for delta-ALA synthase).

73

Megaloblastic anemia

Macrocytic anemia. It occurs due to impaired DNA synthesis, leading to maturation of nucleus of precursor cells in bone marrow delayed relative to maturation in cytoplasm. Findings include RBC macrocytosis, hypersegmented neutrophils, and glossitis.

74

Folate deficiency

Megaloblastic macrocytic anemia. Causes include malnutrition (eg alcoholics), malabsorption, drugs (eg methotrexate, trimethoprim, phenytoin), and increase requirement (eg hemolytic anemia and pregnancy). Findings include an increase in homocysteine and normal methylmalonic acid. There are no neurologic symptoms (vs B12 deficiency).

75

B12 (cobalamin) deficiency

Megaloblastic macrocytic anemia. Causes include insufficiency intake (eg veganism), malabsorption (eg Crohn disease), pernicious anemia, Diphyllobothrium latum (fish tapeworm), gastrectomy. Findings include an increase in homocysteine and methylmalonic acid. Neurologic symptoms include subacute combined degeneration (due to involvement of B12 in fatty acid pathways and myelin synthesis), which affects the spinocerebellar tract, lateral corticospinal tract, and dorsal column dysfunction.

76

Orotic aciduria

Megaloblastic macrocytic anemia. Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) due to a defect in UMP synthase. It is autosomal recessive. It presents in children as failure to thrive, developmental delay, and megaloblastic anemia refractory to folate and B12. There is no hyperammonemia (vs ornithine transcarbamylase deficiency, which has an increase orotic acid with hyperammonemia). Findings include orotic acid in urine. Treatment includes uridine monophosphate to bypass mutated enzyme.

77

Nonmegaloblastic macrocytic anemias

Macrocytic anemia in which DNA synthesis is unimpaired. Causes includes alcoholism, liver disease, hypothyroidism, and reticulocytosis. Findings include, RBC macrocytosis without hypersegmented neutrophils.

78

Normocytic normochromic anemia

Normocytic, bormochromic anemias are classified as nonhemolytic or hemolytic. The hemolytic anemias are further classified according to the cause of the hemolysis (intrinsic vs extrinsic to the RBC) and by location of the hemolysis (intravascular vs extravascular).

79

Intravascular hemolysis

Normocytic normochromic anemia. Findings include a decrease in haptoglobin, an increase in LDH, schistocytes, and reticulocytes on blood smear. Characteristic include hemoglobinuria, hemosiderinuria, and urobilinogen in urine. Notable causes include mechanical hemolysis (eg prosthetic valve), paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemias.

80

Extravascular hemolysis

Normocytic normochromic anemia. Macrophages in spleen clear RBCs. Findings include spherocytes in peripheral smear, an increase in LDH, no hemoglobinuria. hemosiderinuria, an increase in unconjugated bilirubin, which can cause jaundice.

81

Anemia of chronic disease

Nonhemolytic, normocytic anemia. Inflammation leads to an increase in hepcidin, which is released by the liver and binds ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron transport. The increase in hepcidin causes a decrease in release of iron from macrophages. It is associated with conditions like SLEm rheumatoid arthritis, neoplastic disorders, and chronic kidney disease. Findings include a decrease in iron and TIBC and an increase in ferritin. It can become microcytic anemia. Treatment includes EPO in chronic kidney disease only.

82

Aplastic anemia

Normocytic normochromic anemia. It is caused by failure or destruction of myeloid stem cells due to: radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites); viral agents (parvocirus B19, EBV, HIV, HCV), Faconi anemia (DNA repair defect); idiopathic (immune mediated, primary stem cell defect), may follow acute hepatitis. Pancytopenia is characterized by severe anemia, leukopenia, and thrombocytopenia. There is normal cell morphology, but hypocellular bone marrow with fatty infiltration (dry bone marrow tap). Symptoms include malaise, pallor, purpura, mucosal bleeding, petechiae, and infection. Treatment includes withdrawal of offending agent, immunosuppressive regimens (eg antit-hymocyte globulin, cyclosporine), bone marrow allograft, RBC/platelet transfusion, bone marrow stimulation (eg GM-CSF).

83

Hereditary spherocytosis

Extravascular hemolytic normocytic intrinsic anemia. It occurs due to a defect in proteins interacting with RBC membrane skeleton and plasma membrane (eg ankyrin, band 3, protein 4.2, spectrin). This results in small round RBCs with less surface area and no central pallor (resulting in an increase in MCHC and red cell distribution width), which causes premature removal by spleen. Findings includes splenomegaly, aplastic crisis (eg due to parvovirus B19 infection). Labs include a positive osmotic fragility test and a normal to decrease in MCV. with an abundance of cells. Treatment includes splenectomy.

84

G6PD deficiency

Extravascular and intravascular intrinsic hemolytic normocytic anemia. It is the most common enzymatic disorder of RBCs. It is x-linked recessive. A defect in G6PD leads to a decrease in glutathione, which makes RBCs more susceptible to oxidant stress. Hemolytic anemia occurs following oxidant stress (eg sulfa drugs, antimalarials, infections, fava beans). Clinical findings include back pain, hemoglobinuria a few days after oxidant stress. A blood smear shows RBCs with heinz bodies and bite cells. "Stress makes me eat bites of fava beans with Heinz ketchup.

85

Pyruvate kinase deficiency

Extravascular intrinsic hemolytic normocytic anemia. It is autosomal recessive. A defect in pyruvate kinase, which catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP, yielding one molecule of pyruvate and one molecule of ATP, decreases ATP, causing RBCs to be rigid. It presents as hemolytic anemia in a newborn.

86

HbC defect

Extravascular intrinsic hemolytic normocytic anemia. Occurs due to a glutamic acid to lysine mutation in beta-globlin. Patients with HbSC (one of each mutant gene) have milder disease than HbSS.

87

Paroxysomal nocturnal hemoglobinuria

Intravascular intrinsic hemolytic normocytic anemia. An increase in complement-mediated RBC lysis due to an impairment in the synthesis of GPI anchor for decay-accelerating factor that protects RBC membrane from complement. This is due to an acquired mutation in a hematopoietic stem cell. There are also an increase incidence of acute leukemias. There is a triad of negative coombs hemolytic anemia, pancytopenia, and venous thrombosis. Labs show negative CD55/59 RBCs on flow cytometry. Treatment includes eculizumab (terminal complement inhibitor).

88

Sickle cell anemia

Extravascular intrinsic hemolytic normocytic anemia. HbS point mutation causes a single amino acid replacement in the beta chain (a substitution of glutamic acid with valine). Low O2, high altitude, or acidosis can precipitates sickling, which occurs due to deoxygenated HbS polymerization. This causes anemia and vaso-occlusive disease. Newborns are initially asymptomatic due to high levels of HbF and low levels of HbS. Heterozygotes (sickle cell trait) are resistant to malaria. 8% of Africans Americans carry an HbS allele. Xray will show a crew cut on the skull due to marrow expansion from an increase in erythropoiesis (this is also seen in thalassemia). Complications in sickle cell disease include: aplastic crisis (due to parvovirus B19), autosplenectomy (showing Howell-Jolly bodies with blood smear) that has an increase risk of infection from encapsulated bacteria, splenic infarct/ sequestration crisis, salmonella osteomyelitis, painful crises (a vaso-occlusive event, which can manifest as dactylitis (painful swelling of hands/ feet), acute chest syndrome, avascular necrosis, or stroke), renal papillary necrosis (due to a decrease in PO2 in papilla) and microhematuria (medullary infarcts). Diagnosis is based on hemoglobin electrophoresis. Treatment includes hydroxyurea (which increases HbF) and hydration.

89

Autoimmune hemolytic anemia

Extrinsic hemolytic normocytic anemia. Includes warm and cold agglutination. Many warm and cold AIDAs are idiopathic in etiology. Autoimmune hemolytic anemias are usually Coombs positive.

90

Warm agglutinin

Autoimmune hemolytic anemia, IgG mediated. Chronic anemia is seen in SLE and CLL and with certain drugs (eg alpha-methyldopa). Warm weather is Great.

91

Cold agglutinin

Autoimmune hemolytic anemia, IgM mediated. It is an acute anemia triggered by the cold. It is seen in CLL, Mycoplasma pneumonia infections, and infectious Mononucleosis (cold weather is MMMiserable).

92

Direct Coombs test

Anti-Ig antibody (Coombs reagent) is added to patients blood. RBCs agglutinate if RBCs are coated with Ig.

93

Indirect Coombs test

Normal RBCs are added to patient's serum. If serum has anti-RBC surface Ig, RBCs will aggluntinate when Coombs reagent is added.

94

Microangiopathic anemia

Extrinsic hemolytic normocytic anemia. RBCs are damaged when they are passing through obstructed or narrowed vessel lumina. It is seen in DIC, TTP/HUS, SLE, and malignant hypertension. Schistocytes (helmet cells) are seen on blood smear due to mechanical destruction of RBCs.

95

Infections causing anemia

Extrinsic hemolytic normocytic anemia. Malaria or babesia among others can cause an increase destruction of RBCs.

96

Lab values seen in iron deficient anemia

A decrease in serum iron, an increase in transferrin or TIBC, a decrease in ferritin, and a large decrease in the precent of transferrin saturation (serum iron/ TIBC)

97

Lab values seen in anemia in chronic disease

A decrease in serum iron, a decrease in transferrin or TIBC, an increase in ferritin, and no change in the precent of transferrin saturation (serum iron/ TIBC)

98

Lab values seen in anemia due to hemochromatosis

An increase in serum iron, a decrease in transferrin or TIBC, an increase in ferritin, and a large increase in the precent of transferrin saturation (serum iron/ TIBC)

99

Lab values seen in anemia due to pregnancy or OCP use

No change in serum iron, an increase in transferrin or TIBC, no change in ferritin, and a decrease in the precent of transferrin saturation (serum iron/ TIBC)

100

Transferrin

Transports iron in blood.

101

Total iron binding capacity (TIBC)

Indirectly measures transferrin.

102

Ferritin

It is the primary iron storage protein of body.

103

Corticoidsteroid effect on blood cells

Corticosteroids cause neutropenia, despite causing eosinophenia and lymphopenia. Corticosteroids decrease activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation. in contrast, corticosteroids sequester eosinophils in lymph nodes and cause apoptosis of lymphocytes.

104

delta- aminolevulinic acid synthase

The first step in heme synthesis, also the rate limiting step. It catalyzes glycine and succinyl-CoA into delta aminolevulinic acid, with vitamin B6 as a cofactor. It is inhibited by glucose and heme. It is mutated in sideroblastic anemia.

105

delta- aminolevulinic acid dehydratase

The second step in heme synthesis. It occurs in the mitochondria. It converts delta-aminoleculinic acid into porphobilinogen. It is inhibited in lead poisoning.

106

Porphobilinogen deaminase

It is the third step in heme synthesis. It occurs in the mitochondria. It converts porphobilinogen into hydroxymethylbilane. It is mutated in acute intermittent porphyria.

107

Uroporphyrinogen decarboxylase

It is the fifth step in heme synthesis and occurs in the mitochondria. It converts uroporphyrinogen III into coproporphyrinogen III. It is mutated in porphyria cutanea tarda

108

Ferrochelatase

It is the 7th step in heme synthesis and occurs in the mitochondria. It converts protoporphyrin into heme by incorporating Fe. It is inhibited by lead poisoning.

109

Lead poisoning

The affected enzyme is ferrochelatase and ALA dehydratase. Protoporphyrin and delta-ALA becomes accumulated in the blood. It presents is microcytic anemia (showing basophilic stippling) and GI and kidney disease. It often occurs in children due to exposure to lead paint, which leads to mental deterioration. In adults, it often occurs due to environmental exposure (eg batteries or ammunition), which causes headache, memory loss, and demyelination.

110

Acute intermittent porphyria

Porphobilinogen deaminase is mutated. Porphobilinogen, delta ALA, and coporphobilinogen accumulates in urine. Symptoms include (the 5P's): painful abdomen, port wine colored urine, polyneuropathy, psychological disturbances, and precipitated by drugs (eg cytochrome P-450 inducers), alcohol, and starvation. Treatment includes glucose and heme, which inhibit ALA synthase.

111

Porphyria cutanea tarda

Uroporphyrinogen decarboxylase is the mutated enzyme. Uroporphyrin becomes accumalted in urine, causing the urine to turn tea colored. Symptoms include blistering cutaneous photosensitivity. It is the most common porphyria.

112

Iron poisoning

There is a high mortality rate with accidental ingestion by children (adult iron tablets may look like candy). Cell death occurs due to peroxidation of membrane lipids. Symptoms include nausea, vomiting, gastric bleeding, lethargy, and scarring leadingy to GI obstruction. Treatment involve chelation (eg IV deferoxamine, oral deferasirox) and dialysis.

113

Prothrombin time (PT)

It tests the function of common and extrinsic pathway (factors I, II, V, VII, and X). A defect causes an increase in PT

114

Partial thromboplastin time (PTT)

It tests the function of the common and intrinsic pathway (all factors except VII and XIII). A defect causes an increase in PTT.

115

Hemophilia A

An intrinsic pathway coagulation defect in factor VIII, leading to an increase in PTT. It is x-linked recessive.

116

Hemophilia B

An intrinsic pathway coagulation defect in factor IX, leading to an increase in PTT. It is x-linked recessive.

117

Hemophilia C

An intrinsic pathway coagulation defect in factor XI, leading to an increase in PTT. It is autosomal recessive.

118

Macrohemorrhage in hemophilia

There can be hemarthroses (bleeding into the joints, such as knee), easy bruising, bleeding after trauma or surgery (eg dental procedures).

119

Treatment of hemophilia

Desmopressin and factor VIII concentrate (A); factor IX concentrate (B); or factor XI concentrate (C).

120

Vitamin K deficiency

Both PT and PTT increases. It causes a general coagulation defect. Bleeding time remains normal. There is a decrease in activation factors II, VII, IX, X, protein C, and protein S.

121

Platelet disorders

Defects in platelet plug formation causes there to be an increase in bleeding time (BT). Platelet abnormalities leads to microhemorrhage, which causes mucous membrane bleeding, epistaxis, petechiae, purpura, an increase in bleeding time, and possibly decreased platelet count.

122

Bernard Soulier syndrome

Due to a defect in platelet plug formation. There are large platelets. A decrease in GpIb causes there to be a defect in platelet to vWF adhesion. There is no agglutination on ristocetin cofactor assay. Platelet count is normal or decreased. Bleeding time is increased.

123

Glanzmann thrombasthenia

A defect in platelet plug formation. A decrease in GpIIb/IIIa leads to a defect in platelet to platelet aggregation. Labs will show no platelet clumping on blood smear. There is agglutination with ristocetin cofactor assay. There is no change in platelet count and an increase in bleeding time.

124

Immune thrombocytopenia

There are anti-Gp IIb/IIIa antibodies leading to splenic macrophage consumption of platelet-antibody complex. It is commonly due to viral illness. There are an increase in megakaryocytes on bone marrow biopsy. Platelet count is reduced and bleeding time is increased. Treatment includes steroids, intravenous immunoglobulin.

125

Thrombotic thrombocytopenic purpura

There is inhibition or deficiency of ADAMTS 13 (vWF metalloprotease), which causes there to be a decrease in degradation of vWF multimers. An increase in in large vWF multimers leads to an increase in platelet adhesion, causing platelet aggregation and thrombosis. Labs show schistocytes and an increase in LDH. Symptoms include a pentad of neurologic and renal symptoms, fever, thrombocytropenia, and microangiopathic hemolytic anemia. Platelet count decreases and bleeding time increases. treatment include plasmapheresis and steroids.

126

von Willebrand disease

It is an intrinsic pathway coagulation defect due to a decrease in vWF leading to a defect in platelet to vWF adhesion, which increases PTT. vWF normally acts to carry/ protect factor VIII. There is a defect in platelet plug formation because a decrease in vWF causes there to be a defect in platelet to vWF adhesion. It is autosomal dominant. It is mild but is the most common inherited bleeding disorder. It is diagnosed in most cases by ristocetin cofactor assay (a decrease in agglutination is diagnostic). Platelet count and PT are normal. Bleeding time and PTT are increased.

127

DIC

It occurs due to widespread activation of clotting factors causes there to be a deficiency in clotting factor, which increases bleeding state. Causes include Sepsis (gram-negative), Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, and Transfusion (STOP Making New Thrombi). Labs will show schistocytes, an increase in fibrin split products (D-dimers), a decrease in fibrinogen, and a decrease in factors V and VIII. Platelet count in decreased. Bleeding time, PT, and PTT are all increased.

128

Antithrombin deficiency

An inherited deficiency of antithrombin. It has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following heparin administration. It can also be acquired due to renal failure/ nephrotic syndrome, causing there to be antithrombin loss in urine leading there to be a decrease inhibition of factors IIa and Xa.

129

Factor V Leiden

Due to production of mutant factor V that is resistant to degradation by activated protein C. It is the most common cause of inherited hypercoagulability in whites.

130

Protein C or S deficiency

Due to a decrease in ability to inactivate factors Va and VIIIa. There is an increase risk of thrombotic skin necrosis with hemorrhage following administration of warfarin. Clinical symptoms will show skin and subcutaneous tissue necrosis after warfarin administration. Protein C Cancels Coagulation.

131

Prothrombin gene mutation

Due to mutation in 3' untranslated region causes there to be an increase in production of prothrombin, increasing plasma levels and venous clots.

132

Packed RBCs transfusion therapy

It increases hemoglobin and O2 carrying capacity. It is used in acute blood loss and severe anemia.

133

Platelets transfusion therapy

It increases platelet count (by about 5000/mm3/unit). It is used to stop significant bleeding for thrombocytopenia and qualitative platelet defects.

134

Fresh frozen plasma transfusion therapy

It increases coagulation factor levels. It is used to treat DIC, cirrhosis, and immediate warfarin reversal.

135

Cryoprecipitate

It contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin. It is used to treat coagulation factor deficiencies involving fibrinogen and factor VIII.

136

Risks associated with blood transfusion

Risks include infection transmission (low), transfusion reactions, iron overload, hypocalcemia (citrate is a Ca chelator), and hyperkalemia (RBCs may lyse in old blood units).

137

Leukemia

Lymphoid or myeloid neoplasm with widespread involvement of bone marrow. Tumor cells are usually found in peripheral blood.

138

Lymphoma

A discrete tumor mass arising from lymph nodes. Presentations often blur types of lymphoma.

139

Leukemoid reaction

An acute inflammatory response to infection. There is an increase in WBC count with neutrophil and neutrophil precursors such as band cells (a left shift). There is also an increase in leukocyte alkaline phosphatase (LAP). In contrast with CML which also has an increase in WBC with left shift but a decrease in LAP.

140

Hodgkin lymphoma

It is characterized by localized single group of nodes. Extranodal manifestations are rare. Spread is contiguous (stage is the strongest predictor of prognosis). Prognosis is much better than non-Hodgkin lymphoma. It is characterized by Reed-Sternberg cells. There is a bimodal distribution, young adulthood and over 55 years. It is more common in men except for the nodular sclerosing type. It is strongly associated with EBV. There are constitutional (B) signs/ symptoms, including low-grade fever, night sweats, and weight loss.

141

Non-hodgkin lymphoma

It is characterized by multiple, peripheral nodes. Extranodal involvement is common. It spreads noncontiguous. The majority involve B cells (except those of lymphoblastic T-cell origin). Peak incidence for certain subtypes is from 20-40 years old. It may be associated with HIV and autoimmune disease. There are fewer constitutional signs/ symptoms than hodgkin lymphoma.

142

Reed Sternberg cells

Distinctive tumor giant cells seen in Hodgekin disease; it is binucleate or bilobed with the 2 halves as mirror images (owl eyes). RS cells are CD15+ and CD30+ of B cell origin. They are necessary but not sufficient for diagnosis of Hodgkin disease. There is a better prognosis with strong stomal or lymphocytic reaction against RS cells. The most common type that causes RS cells is nodular sclerosing form (affects women and men equally). The lymphocyte mixed or depleted forms have the worse prognosis.

143

Burkett lymphoma

A non-Hodhkin lymphoma of mature B cells. Occurs in adolescents or young adults. t(8;14) translocation of c-myc (8) and heavy chain Ig (14). Histology shows "Starry sky" appearance, sheets of lymphocytes with interspersed macrophages. It is associated with EBV. It is associated with jaw lesion in endemic form in Africa; pelvic and abdomen in sporadic form.

144

Diffuse large B-cell lymphoma

A non-Hodhkin lymphoma of mature B cells. It usually occurs in older adults, but 20% occurs in children. It is the most common type of non-Hodgkin lymphoma in adults.

145

Follicular lymphoma

A non-Hodhkin lymphoma of mature B cells. It occurs in adults. t(14;18) translocation of heavy chain Ig (14) and BCL-2 (18). There is an indolent course. Bcl-2 inhibits apoptosis. It presents with painless "waxing and waning" lymphadenopathy. Histology shows nodular, small cells, cleaved nuclei.

146

Mantle cell lymphoma

A non-Hodhkin lymphoma of mature B cells. It occur in older males due to a t(11;14) translocation of cyclin D1 (11) and heaving chain Ig (14). Cells express CD5+.

147

Adult T-cell lymphoma

A non-Hodhkin lymphoma of mature T cells. It occurs in adults and is caused by HTLV (human T-lymphotropic virus), which is associated with IV drug abuse. Adults will present with cutaneous lesions; it especially effects populations in Japan, West Africa, and the Caribbean. It causes lytic bone lesions and hypercalcemia.

148

Mycosis fungoides/ Sezary syndrome

A non-Hodhkin lymphoma of mature T cells. It occurs in adults. Mycosis fungoides presents with skin patches/ plaques (cutaneous T-cell lymphoma), characterized by atypical CD4+ cells with "cerebriform" nuclei. It may progress to Sezary syndrome (T-cell leukemia).

149

Multiple myeloma

It is a monoclonal plasma cell (fried egg appearance) cancer that arises in the marrow and produces a large amounts of IgG (55%) or IgA (25%). It is the most common primary tumor arising within bone in people over the age 40-50 years. It is associated with an increase susceptibility to infection, primary amyloidosis (AL), punched out lytic bone lesions on x-ray (leading to hypercalcemia), M spike (due to IgG) on serum protein electrophoresis, Ig light chains in urine (Bence Jones protein), Rouleaux formation (RBC stacked like poker chips in blood smear). There are numerous plasma cells with "clock face" chromatin and intracytoplasmic inclusions containing immunoglobulin. Symptoms include CRAB: hyperCalcermia, Renal involvement, Anemia, Bone lytic lesions/ Back pain. Multiple Myeloma= Monoclonal M protein spike.

150

Monoclonal gammopathy of undetermined significance (MGUS)

A monoclonal expansion of plasma cells. It is asymptomatic and made lead to multiple myeloma. There are no "CRAB" findings (hyperCalcermia, Renal involvement, Anemia, Bone lytic lesions/ Back pain). Patients with MGUS develop multiple myeloma at a rate of 1-2% per year.

151

Waldenstrom macroglobulinemia

It can be distinguished from multiple myeloma because the M spike is due to IgM, which leads to hyperviscosity syndrome (eg blurred vision, Raynaud phenomenon). There are no CRAB findings (hyperCalcermia, Renal involvement, Anemia, Bone lytic lesions/ Back pain)

152

Myelodysplastic syndromes

They are stem cell disorders involving ineffective hematopoiesis leading to defects in cell maturation of all nonlymphoid lineages. It is caused by de novo mutations or environmental exposure (eg radiation, benzene, chemotherapy). There is a risk of transformation to AML.

153

Pseudo Pelger Huet anomaly

Neutrophils are seen with bilobed nuclei. It is typically seen after chemotherapy.

154

Leukemias

It is unregulated growth and differentiation of WBCs in bone marrow, causing the marrow to fail, leading to anemia (a decrease in RBCs), infections (due to a decrease in mature WBCs), and hemorrhage (due to a decrease in platelets). There can be an increase or a decrease in the number of circulating WBCs.

155

Acute lymphoblastic leukemia/ lymphoma (ALL)

A lymphoid neoplasm. Occurs in those under the age of 15. T-cell can present as mediastinal mass (presenting as a SVC-like syndrome). It is associated with Down syndrome. Peripheral blood and bone marrow will have a large increase in lymphoblasts (purple stained with coarser chromatin and fewer nucleoli than myeloblasts). Markers include TdT+ (a marker of pre T and pre B cells) and CD10+ (pre B cells only). It is the most responsive leukemia to therapy. It may spread to CNS and testes. t(12,21) has a better prognosis.

156

Small lymphocytic lymphoma (SLL)/ chronic lymphocytic leukemia (CLL)

A lymphoid neoplasm. It occurs in those over the age of 60. It is the most common leukemia in adults. It is a CD20+ and CD5+ B-cell neoplasm. It is often asymptomatic and progresses slowly. Peripheral blood smear will show smudge cells. It is associated with autoimmune hemolytic anemia. SLL is the same as CLL except CLL has an increase in peripheral blood lymphocytosis or bone marrow involvement.

157

Hairy cell leukemia

A lymphoid neoplasm. It occurs in adults. It is a mature B-cell tumor in the elderly. Cells have a filamentous, hair-like projections. It causes marrow fibrosis which causes there to be a dry tap on aspiration. It stains tartate-resistant acid phosphatase positive (TRAP). TRAP stain has largely been replaced with flow cytometry. Treatment includes cladribine (a purine analog) and pentostatin (a purine analog).

158

Acute myelogenous leukemia (AML)

A myeloid neoplasms. The median age of onset is 65 years. Cells have Auer rods. Peroxidase positive cytoplasmic inclusions are seen mostly in M3 AML. There is a large increase in circulating myeloblasts on peripheral smear. Risk factors include prior exposure to alkylating chemotherapy, radiation, myeloproliferative disorders, Down syndrome. t(15;17) translocation occurs in M3 AML subtype and responds to all-trans retinoic acid (vitamin A), which can restore the differentiation capacity of leukemic promyelocytes. DIC is a common presentation of M3 AML.

159

Chronic myelogenous leukemia (CML)

A myeloid neoplasms. The peak incidence is 45-85 years of age with the median age at diagnosis being 64 years. It is defined by the Philadelphia chromosome (t(9;22), BCR-ABL). It is marked by myeloid stem cell proliferation and presents with an increase in neutrophils, metamyelocytes (boomerang shaped), and basophils. There is also splenomegaly. It may accelerate and transform to AML or ALL (blast crisis). There is very low LAP (Leukocyte Alkaline Phosphatase) as a result of low activity in mature granulocytes (vs leukemoid reaction, in which LAP is increased). It responds to imatinib (a small molecule inhibitor of the bcr-abl tyrosine kinase).

160

t(8,14)

Burkitt lymphoma (c-myc activation)

161

t(9; 22)

Philadelphia chromosome. CML (BCR-ABL hybrid). Philadelphia CreaML cheese.

162

t(11;14)

Mantle cell lymphoma (cyclin D1 activation)

163

t(14;18)

Follicular lymphoma (BCL-2 activation)

164

t(15;17)

M3 type of AML. It responds to all-trans retinoic acid.

165

Langerhans cell histiocytosis

A collective group of proliferative disorders of dendritic (Langerhans) cells. It presents in a child as lytic bone lesions and skin rash or as recurrent otitis media with a mass involving the mastoid bone. Cells are functionally immature and do not effectively stimulate primary T cells via antigen presentation. Cells express S-100 (mesodermal origin) and CD1a. Birbeck granules (tennis rackets or rod shaped on EM) are characteristic.

166

Chronic myeloproliferative disorders

They are often overlapping in spectrum. JAK2 is involved in hematopoietic growth factor signaling. JAK2 gene mutation is often found in chronic myeloproliferative disorders except CML, which has BCR-ABL translocation.

167

Polycythemia vera

A chronic myeloproliferative disorder of increased hematocrit and is often associated with JAK2 mutation. It may present as intense itching after a hot shower (due to an increase in basophils). A rare but classic symptom is erythromelagia (severe, burning pain and red-blue coloration) due to episodic blood clots in vessels of the extremities. Secondary polycythemia occurs due to a natural or artificial increase in EPO levels.

168

Essential thrombocytosis

A chronic myeloproliferative disorder similar to polycythemia vera but is specific for overproduction of abnormal platelets, which causes bleeding and thrombosis. Bone marrow contains enlarged megakaryocytes.

169

Myelofibrosis

A chronic myeloproliferative disorder, which involves obliteration of bone marrow due to an increase in fibroblast activity is response to proliferation of monoclonal cell lines. Teardrop RBCs and immature forms of the myeloid line are seen in a peripheral blood smear. Bone marrow is crying because its fibrosed and is a dry tap. It is often associated with massive splenomegaly.

170

Lab findings with polycythemia vera

There are increased RBCs, WBCs, and platelets. There is a JAK2 mutation and no Philadelphia chromosome. Plasma volume is increased. RBC mass is greatly increased. There is no change in O2 saturation. EPO levels decrease due to negative feedback suppressing renal EPO production.

171

Lab findings with essential thrombocytosis

There are no changes in RBCs and WBCs. There is an increase in platelets. There is a JAK2 mutation (30-50%) and no Philadelphia chromosome.

172

Lab findings with myelofibrosis

There is a decrease in RBCs. The amount of WBCs and platelets are variable. There is a JAK2 mutation (30-50%) and no Philadelphia chromosome.

173

Lab findings with CML

There is a decrease in RBCs and an increase in WBCs and platelets. There is a Philadelphia chromosome and no JAK2 mutation.

174

Lab findings with relative polycythemia

Occurs due to a decrease in plasma volume (dehydration and burns). There are no changes in RBC mass, O2 saturation, and EPO levels.

175

Lab findings with appropriate absolute polycythemia

An appropriate compensatory response to lung disease, congenital heart disease or high altitude. There is no change in plasma volume. RBC mass and EPO levels are increased while O2 saturation decreases.

176

Lab findings with inappropriate absolute polycythemia

An inappropriate compensatory response to renal cell carcinoma, hepatocellular carcinoma, hydronephrosis. It occurs due to ectopic EPO production. There is no change in plasma volume and O2 saturation. RBC mass and EPO levels are increased.

177

Mechanism of heparin

An activator of antithrombin, which decreases thrombin and factor Xa. It has a short life.

178

Clinical use of heparin

It is used for immediate anticoagulation for pulmonary embolism (PE) and acute coronary syndrome, MI, and deep venous thrombosis (DVT). It is used during pregnancy because it does not cross the placenta. It is followed with PTT.

179

Heparin toxicity

It causes bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For rapid reversal (antidote), use protamine sulfate (positively charged molecule that binds negatively charged heparin).

180

Low molecular weight heparin

For example enoxaparin and dalteparin. It acts more on factor Xa with better bioavailability and 2-4 times longer half life. It can be administered subcutaneously and without laboratory monitoring. It is not easily reversible.

181

Fondaparinux

It acts more on factor Xa with better bioavailability and 2-4 times longer half life. It can be administered subcutaneously and without laboratory monitoring. It is not easily reversible.

182

Heparin induced thrombocytopenia (HIT)

The developement of IgG antibodies against heparin bound platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets, which causes thrombosis and thrombocytopenia.

183

Argatroban

It inhibits thrombin directly. It is an alternative to heparin for anticoagulating patients with HIT.

184

Bivalirudin

It is related to hirudin, the anticoagulant used by leeches. It inhibits thrombin directly. It is an alternative to heparin for anticoagulating patients with HIT.

185

Mechanism of warfarin

It interferes with gamma-carboxylation of vitamin K-dependent clotting factors II, VII, IX, and X, and proteins C and S. Metabolism is affected by polymorphisms in the gene for vitamin K epoxide reductase complex (VKORC1). In laboratory assay, has an effect on EXtrinsic pathway and increases PT. There is a long half life. The EX-PresidenT went to war(farin).

186

Clinical use of warfarin

It is used for chronic anticoagulation (eg venous thromboembolism prophylaxis, and prevention of stroke in atrial fibrillation). It is not used in pregnant women (because warfarin, unlike heparin, crosses the placenta). It is monitored with PT/INR.

187

Warfarin toxicity

Includes bleeding, teratogenic, skin/ tissue necrosis, drug-drug interactions. Proteins C and S have shorter half lives than clotting factors II, VI, IX, and X, resulting in an early transient hypercoagulability with warfarin use. Skin/ tissue necrosis is believed to be due to small vessel microthromboses. For reversal of warfarin, give vitamin K. For rapid reversal, give fresh frozen plasma. Heparin bridging is frequently used when starting warfarin. Heparin's activation of antithrombin enables anticoagulation during the initial, transient hypercoagulable state caused by warfarin and reduces the risk of recurrent venous thromboembolism and skin/ tissue necrosis.

188

Heparin vs warfarin

Heparin's structure is large, anionic, acidic polymer, while warfarin is a small amphipathic molecule. Heparin is administered parenteral while warfarin is oral. Heparin site of action is in the blood, while warfarin acts in the liver. Heparin's onset is rapid, while warfarin is slower and limited by the half-lives of normal clotting factors. The duration of action is acute in heparin and chronic in warfarin. Heparin inhibits coagulation in vitro but not with warfarin. Heparin is motored with PPT, while warfarin is monitored with PT/INR. Heparin does not cross the placenta while warfarin does.

189

Apixaban

A direct factor Xa inhibitor. Clinical use is treatment and prophylaxis for DVT and PE; stroke prophylaxis in patients with atrial fibrillation. Oral agents do not require coagulation monitoring. Toxicity includes bleeding (no reversal agent available.

190

Rivaroxaban

A direct factor Xa inhibitor. Clinical use is treatment and prophylaxis for DVT and PE; stroke prophylaxis in patients with atrial fibrillation. Oral agents do not require coagulation monitoring. Toxicity includes bleeding (no reversal agent available.

191

Alteplase

tPA. It helps with the conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. They will increase PT, PTT with no change in platelet count. It is used in early MI, early ischemic stroke, direct thrombolysis of severe PE. Toxicities include bleeding. It is contraindicated in patientswith active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.

192

Reteplase

rPA. It helps with the conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. They will increase PT, PTT with no change in platelet count. It is used in early MI, early ischemic stroke, direct thrombolysis of severe PE. Toxicities include bleeding. It is contraindicated in patientswith active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.

193

Streptokinase

It helps with the conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. They will increase PT, PTT with no change in platelet count. It is used in early MI, early ischemic stroke, direct thrombolysis of severe PE. Toxicities include bleeding. It is contraindicated in patientswith active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.

194

Tenecteplase

TNK-tPA. It helps with the conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. They will increase PT, PTT with no change in platelet count. It is used in early MI, early ischemic stroke, direct thrombolysis of severe PE. Toxicities include bleeding. It is contraindicated in patientswith active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.

195

Aspirin

It irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) enzyme by covalent acetylation. Platelets cannot synthesize new enzyme so the effect lasts until new platelets are produced, which causes an increase in bleeding time and a decrease of TXA2 and prostaglandins. There is no effect on PT or PTT. It is used as an antipyretic, analgesic, anti-inflammatory, and antiplatelet (by decreasing aggregation).

196

Aspirin toxicity

Toxicities include gastric ulceration, tinnitus (CNVIII). Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding. Reye syndrome can occur in children with viral infection. Overdose initially causes hyperventilation and respiratory alkalosis, but transition to mixed metabolic acidosis-respiratory alkalosis.

197

Clopidogral

It inhibits platelet aggregation by irreversibly blocking ADP receptors. It prevents expression of glycoproteins IIb/IIIa on platelet surface. It is used for acute coronary syndrome; coronary stenting. There is a decrease incidence or recurrence of thrombotic stroke. Toxicities include thrombotic thrombocytopenic purpura (TTP).

198

Prasugrel

It inhibits platelet aggregation by irreversibly blocking ADP receptors. It prevents expression of glycoproteins IIb/IIIa on platelet surface. It is used for acute coronary syndrome; coronary stenting. There is a decrease incidence or recurrence of thrombotic stroke. Toxicities include thrombotic thrombocytopenic purpura (TTP).

199

Ticagrelor

It inhibits platelet aggregation by reversibly blocking ADP receptors. It prevents expression of glycoproteins IIb/IIIa on platelet surface. It is used for acute coronary syndrome; coronary stenting. There is a decrease incidence or recurrence of thrombotic stroke. Toxicities include thrombotic thrombocytopenic purpura (TTP).

200

Ticlopidine

It inhibits platelet aggregation by reversibly blocking ADP receptors. It prevents expression of glycoproteins IIb/IIIa on platelet surface. It is used for acute coronary syndrome; coronary stenting. There is a decrease incidence or recurrence of thrombotic stroke. Toxicities include neutropenia and thrombotic thrombocytopenic purpura (TTP).

201

Cilostazol

It is a phosphodiesterase III inhibitor, which increases cAMP in platelets, resulting in inhibition of platelet aggregation. It also causes vasodilation. It is used for intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with aspirin), and angina prophylaxis. toxicities include nausea, headache, facial flushing, hypotension, and abdominal pain.

202

Dipyridamole

It is a phosphodiesterase III inhibitor, which increases cAMP in platelets, resulting in inhibition of platelet aggregation. It also causes vasodilation. It is used for intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with aspirin), and angina prophylaxis. toxicities include nausea, headache, facial flushing, hypotension, and abdominal pain.

203

Abciximab

It binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation. Abciximab is made from monoclonal antibody Fab fragments. It is used for unstable angina, percutaneous transluminal coronary angioplasty. Toxicities include bleeding and thrombocytopenia.

204

Eptifibatide

It binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation. It is used for unstable angina, percutaneous transluminal coronary angioplasty. Toxicities include bleeding and thrombocytopenia.

205

Tirofiban

It binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation. It is used for unstable angina, percutaneous transluminal coronary angioplasty. Toxicities include bleeding and thrombocytopenia.

206

Cancer drugs that inhibit G2

bleomycin, etoposide, teniposide

207

Cancer drugs that inhibit DNA synthesis

etoposide, teniposide, and antimetabolites (azathrioprine, cladribine, cytarabine, 5-fluorouracil, hydroxyurea, methotrexate, 6-mercaptopurine, and 6-thioguanine)

208

Cancer drugs that inhibit mitosis

Microtubule inhibitors (paclitaxel), vinca alkaloids (vinblastine and vincristine)

209

Cancer drugs that inhibit G1

Alkylating agents and nitrosoureas (carmustine, cisplatin, and lomustine)

210

Cancer drugs that decrease thymidine synthesis

Mthotrexate and 5-fluorouracil

211

Cancer drugs that decrease de novo purine synthesis

6-mercaptopurine

212

Cancer drugs that inhibit ribonucleotide reductase

hydroxyurea

213

Cancer drugs that cross link DNA

alkylating agents and cisplatin

214

Cancer drugs that break DNA strands

bleomycin

215

Cancer drugs that intercalates DNA

Dactinomycin and doxorubicin

216

Cancer drugs that inhibit topoisomerase II

Etoposide

217

Cancer drugs that inhibit topoisomerase I

Irinotecan

218

Cancer drugs that inhibit microtubule formation

Vinca alkaloids

219

Cancer drugs that microtubule disassembly

Paclitaxel

220

Azathioprine

A purine (thiol) analog, which decreases de novo purine synthesis. It is activated by HGPRT. It is metabolized into 6-mercaptopurine. It is used in preventing organ rejection, rheumatoid arthritis, IBD, and SLE. It is also used to wean patients off steroids in chronic disease and to treat steroid-refractory chronic disease. Toxicities include myelosuppression, GI, and liver problems. It is metabolized by xanthine oxidase and therefore has an increase toxicity with allopurinol or febuxostat.

221

6-mercaptopurine (6-MP)

A purine (thiol) analog, which decreases de novo purine synthesis. It is activated by HGPRT. It is used in preventing organ rejection, rheumatoid arthritis, IBD, and SLE. It is also used to wean patients off steroids in chronic disease and to treat steroid-refractory chronic disease. Toxicities include myelosuppression, GI, and liver problems. It is metabolized by xanthine oxidase and therefore has an increase toxicity with allopurinol or febuxostat.

222

6-thioguanine (6-TG)

A purine (thiol) analog, which decreases de novo purine synthesis. It is activated by HGPRT. It is used in preventing organ rejection, rheumatoid arthritis, IBD, and SLE. It is also used to wean patients off steroids in chronic disease and to treat steroid-refractory chronic disease. Toxicities include myelosuppression, GI, and liver problems.

223

Cladribine (2-CDA)

It is a purine analog that causes inhibition of DNA polymerase and breaking of DNA strands). It is used to treat Hairy cell leukemia. Toxicities include myelosuppression, nephrotoxicity, and neurotoxicity.

224

Cytarabine (arabinofuranosyl cytidine)

It is a pyrimidine analog that inhibits DNA polyermase. It is used to treat leukemia (AML) and lymphomas. Toxicities include leukopenia, thrombocytopenia, megaloblastic anemia. CYTarabine causes panCYTopenia.

225

5-fluorouracil (5-FU)

A prymidine analog that is bioactivated to 5f-dUMP, which covalently complexes folic acid. This complex that inhibits thymidylate synthase, which decreases dTMP and therefore decreasing DNA synthesis. It is used to treat colon cancer, pancreatic cancer, and basal cell carcinoma (topical). Toxicity includes myelosuppression, which is not reversible with leucovorin (folinic acid).

226

Methotrexate (MTX)

A folic acid analog that competitively inhibits dihydrofolate reductase, which decreases dTMP and thereby decreasing DNA synthesis. It is used to neoplastic conditions such as treat leukemias (ALL), lymphoma, choriocarcinoma, sarcomas. It is also used to treat ectopic pregnancy, medical abortion (with misoprostol), rheumatoid arthritis, psoriasis, IBD, and vasculitis. Toxicities include myelosuppression, which is reversible with leucocorin (folinic acid). It can also cause hepatotoxicity, mucositis (eg mouth ulcers), and pulmonary fibrosis.

227

Cancer drugs that inhibit thymidylate synthase

5-fluorouracil (5-FU), which prevents dUMP with CH2-THF being converted into dTMP.

228

Cancer drugs that inhibit dihydrofolate (DHF) reductase

Methotrexate (MTX), which prevents dihydrofolate (DHF) to be converted into tetrahydrofuran (THF)

229

Bleomycin

It induces free radical formation leading to breaks in DNA strands. It is used to treat testicular cancer, Hodgkin lymphoma. Toxicities include pulmonary fibrosis, skin hyperpigmentation, and mucositis. There is minimal myelosuppression.

230

Dactinomycin (actinomycin D)

It intercalates in DNA. It is used to treat Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. It is used for childhood tumors (children ACT out). Toxicity includes myelosuppression.

231

Doxorubicin

It generates free radicals, which intercalate DNA causing breaks in DNA and decreasing replication. It is used to treat solid tumors, leukemia, and lymphomas. Toxicities include cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. It is toxic to tissues following extravastion. Dexrazoxane (iron chelating agent) is used to prevent cardiotoxicity.

232

Daunorubicin

It generates free radicals, which intercalate DNA causing breaks in DNA and decreasing replication. It is used to treat solid tumors, leukemia, and lymphomas. Toxicities include cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. It is toxic to tissues following extravastion. Dexrazoxane (iron chelating agent) is used to prevent cardiotoxicity.

233

Busulfan

It cross links DNA. It is used to treat CML. It is also used to ablate patients bone marrow before bone marrow transplantation. Toxicities include severe myelosuppression (in almost all cases), pulmonary fibrosis, and hyperpigmentation.

234

Cyclophosphamide

It cross-link DNA at guanine N-7. It requires bioactivation by the liver. It is used to treat solid tumors, leukemia, lymphomas. Toxicity includes myelosuppression and hemorrhagic cystitis, which can be partially prevented with mesna (thiol group of mesna binds toxic metabolites).

235

Ifosfamide

It cross-link DNA at guanine N-7. It requires bioactivation by the liver. It is used to treat solid tumors, leukemia, lymphomas. Toxicity includes myelosuppression and hemorrhagic cystitis, which can be partially prevented with mesna (thiol group of mesna binds toxic metabolites).

236

Nitrosoureas (carmustine, lomustine, semustine, streptozocin)

It requires bioactivation. It crosses the blood-brain barrier into the CNS and cross-link DNA. It is used to brain tumors (including glioblastoma multiforme). Toxicities include CNS toxicity (convulsions, dizziness, and ataxia).

237

Paclitaxel and other taxols

It hyperstabilizes polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur). It is TAXing to break down microtubules. It is used to treat ovarian and breast carcinomas. Toxicities include myelosuppression, alopecia, and hypersensitivity.

238

Vincristine

It is a vinca alkaloids that bind beta-tubulin and inhibit its polymerization into microtubules and thereby preventing mitotic spindle formation (M-phase arrest). It is used to treat solid tumors, leukemias, and non-Hodgkin lymphomas. Toxicities include neurotoxicity (areflexia, peripheral neuritis) and paralytic ileus.

239

Vinblastine

It is a vinca alkaloids that bind beta-tubulin and inhibit its polymerization into microtubules and thereby preventing mitotic spindle formation (M-phase arrest). It is used to treat solid tumors, leukemias, and Hodgkin lymphomas. VinBLASTine blasts bone marrow (suppression).

240

Cisplatin

It cross-links DNA. It is used to treat testicular, bladder, ovary, and lung carcinomas. Toxicities include nephrotoxicity and ototoxicity. Amifostine (a free radical scavenger) can prevent the nephrotoxicity and chloride (saline) diuresis.

241

Carboplatin

It cross-links DNA. It is used to treat testicular, bladder, ovary, and lung carcinomas. Toxicities include nephrotoxicity and ototoxicity. Amifostine (a free radical scavenger) can prevent the nephrotoxicity and chloride (saline) diuresis.

242

Etoposide

eTOPOside inhibits TOPOisomerase II, leading to DNA degradation. It is used to treat solid tumors (particularly testicular and small cell lung cancer), leukemias, and lymphomas. Toxicities include include myelosuppression, GI upset, and alopecia.

243

Teniposide

It inhibits topoisomerase II, leading to DNA degradation. It is used to treat solid tumors (particularly testicular and small cell lung cancer), leukemias, and lymphomas. Toxicities include include myelosuppression, GI upset, and alopecia.

244

Irinotecen

It inhibits topoisomerase I and prevents DNA unwinding and replication. It is used to treat colon cancer. Toxicities include severe myelosuppression and diarrhea.

245

Topotecan

It inhibits topoisomerase I and prevents DNA unwinding and replication. It is used to treat ovarian and small cell lung cancer. Toxicities include severe myelosuppression and diarrhea.

246

Hydroxyurea

It inhibits ribonucleotide reductase, leading to a decrease in DNA Synthatesis (S-phase specific). It is used to treat melanoma, CML, sickle cell disease (it increases HbF). Toxicities include severe myelosuppression and GI upset.

247

Prednisone

There are various mechanism of action including binding of intracytoplasmic receptor and altering gene transcription. It is one of the most commonly used glucocorticoids in cancer chemotherapy. It is used to treat CLL, non-Hodgkin lymphoma (part of combination chemotherapy regimen). Also is used as an immunosuppressants (eg in autoimmune disease). Toxicities include cushing like symptoms, weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosism hypertension, peptic ulcers, hyperglycemia, and psychosis.

248

Prednisolone

There are various mechanism of action including binding of intracytoplasmic receptor and altering gene transcription. It is one of the most commonly used glucocorticoids in cancer chemotherapy. It is used to treat CLL, non-Hodgkin lymphoma (part of combination chemotherapy regimen). Also is used as an immunosuppressants (eg in autoimmune disease). Toxicities include cushing like symptoms, weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosism hypertension, peptic ulcers, hyperglycemia, and psychosis.

249

Bevacizumab

It is a monoclonal antibody against VEGF, which inhibits angiogenesis. It is used to treat solid tumors such as colorectal cancer and renal cell carcinoma. Toxicity includes hemorrhage, blood clots, and impaired wound healing.

250

Erlotinib

It inhibits EGFR tyrosine kinase and is used to treat non-small cell lung carcinoma. Toxicity includes rash.

251

Imatinib

It is a tyrosine kinase inhibitor of BCR-ABL (Philadelphia chromosome fusion gene in CML) and c-kit (common in GI stromal tumors). Toxicity includes fluid retention.

252

Rituximab

It is a monoclonal antibody against CD20, which is found on most B-cell neoplasms. it is used to treat non-hodgkin lymphoma, CLLm IBD, rheumatoid arthritis. Toxicity includes an increase risk of progressive multifocal leukoencephalopathy.

253

Tamoxifen

It is a selective estrogen receptor modulator (SERMs)- a receptor antagonist in breast and an agonist in bone. It blocks the binding of estrogen to ER positive cells. It is used to treat breast cancer and prevention. There is toxicity due to it being a partial agonist in endometrium, which increases the risk of endometrial cancer and causes hot flashes.

254

Raloxifene

It is a selective estrogen receptor modulator (SERMs)- a receptor antagonist in breast and an agonist in bone. It blocks the binding of estrogen to ER positive cells. It is used to prevent osteoporosis. There is no increase in endometrial carcinoma because it is an estrogen receptor antagonist in endometrial tissue.

255

Trastuzumab (Herceptin)

It is a monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor. It helps kill cancer cells that overexpress HER-2, through inhibition of HER-2 initiated cellular signaling and antibody-dependent cytotoxicity. It is used to treat HER-2 positive breast cancer and gastric cancer. It can cause cardiotoxicity (Heartceptin damages the heart).

256

Vemurafenib

It is a small molecule inhibitor of BRAF oncogene positive melanoma and is used to treat metastatic melanoma.

257

Cancer drugs that cause acoustic nerve damage and nephrotoxicity

Cisplatin and carboplatin

258

Cancer drugs that cause peripheral neuropathy

Vincristine

259

Cancer drugs that cause pulmonary fibrosis

Bleomycin and busulfan

260

Cancer drugs that cause cardiotoxicity

Doxorubicin and trastuzumab

261

Cancer drugs that cause hemorrhagic cystitis

Cyclophosphamide

262

Cancer drugs that cause myelosuppression

Methotrexate, 5-FU and 6-MP