Lecture 1 (hem/onc)-Exam 1 Flashcards

Question

What does this show of a pt with many blood transfusion?

Answer 1

* Inherited form of iron overload * Due to mutation in HFE gene on chromosome 6; predominant in those of Northern European descent (res disorder) * Usually asymptomatic until age 40-60 years * Men > women

Answer 2

* Same signs/symptoms (except bronze skin-> iron in skin+melanin production), lab findings, & radiological findings as acquired form of hemochromatosis * Increase ferritin and liver enzymes * Treatment: therapeutic phlebotomy

Answer 3

1. Blood flow: dilutes and washes away any clotting factors that get activated (so it does not go overboard) 2. Normal levels of protein C, protein S, antithrombin, & tissue factor pathway inhibitor 3. Fibrinolytic system: breaks down the clot once it’s formed | If one of these fail, you can a clot

Answer 4

* The obstruction of blood flow due to formation of clot (thrombus) * Results in tissue anoxia & damage * As many as 900,000 people affected by venous thromboembolism in the U.S. each year & 60,000-100,000 die as a result * Coronary heart disease remains the number one cause of death in the U.S. * Cerebral vascular disease remained the 5th leading cause of death in the U.S. as of 2020

Answer 5

* **Stasis of blood flow**: immobilization, bed rest, extended travel * **Endothelial injury**: trauma, surgery * **Hypercoagulability**: imbalance of protein in blood

Answer 6

* Pregnancy and postpartum * Smoking * surgery * estrogen use (birth control and hormone replacement) * Cancer (active)

Answer 7

* Due to the production of substances with procoagulant activity, such as tissue factor and cancer procoagulant * Associated with both solid tumor and blood cancers * ~20% of patients with symptomatic DVT have a known active malignancy

Answer 8

a cancer-associated migratory thrombophlebitis (superifical blood clot

Answer 9

* Due to tissue injury & additive effects of anesthesia, pain, hypothermia, bleeding and fasting->lead to increases in cytokines, factor VIII, vWF, fibrinogen, platelet count & reactivity * Risk increases with more invasive and longer procedures * >50% risk with some orthopedic (hip+knee replacement) & cardiothoracic surgeries (open chest)-> give preventive anticog thearpy

Answer 10

* Associated with progressive increases in several coagulation factors, including factors I, II, VII, VIII, IX, and X, along with a decrease in protein S * Symptoms may overlap those of pregnancy (leg or abdominal swelling, shortness of breath), delaying diagnosis

Answer 11

* Autoimmune disorder (ex lupus) * Diagnosed by antibody testing: immunoassays for cardiolipin, beta2-glycoprotein (GP) I, and lupus anticoagulant (LA) phenomenon * Arterial thromboses possible * Pregnancy complications: fetal loss, placental insufficiency, preeclampsia * Thrombocytopenia present in ~25% of patients with APS

Answer 12

* Definition: Platelet count greater than 450,000/µL * 90% of cases are secondary, also called “reactive”: infection, inflammation (including cancer), iron deficiency, or post-splenectomy * 10% are due to myeloproliferative disorders * Possibly carries increased risk for thromboses if **>1 million/µL**

Answer 13

* Most venous clots are deep vein thrombosis (DVT) of an extremity or pulmonary embolism (PE) * PE is usually embolus of lower extremity DVT * Collectively called venous thromboembolism (VTE)-> both DVT and PE * ≥ 2 risk factors in majority of cases

Answer 14

+Risk factors present (“provoked”) Symptoms * Swelling of limb (usually in lower extremity) &/or progressive, constant, unilateral calf pain/cramping Physical exam findings * Pitting edema of an extremity (unilateral or unequal), rubor, calor, calf tenderness, superficial venous dilation, positive Homan’s sign (pain in cald when dorsiflex foot)

Answer 15

lines place: PICC, central line, port

Answer 16

1. Obtain history (hx of DVT) and physical exam- consider Homan’s sign 2. Calculate Well’s score 3. If appropriate, check D dimer level 4. If elevated D dimer level or high clinical suspicion, confirm with ultrasound with **venous doppler study of the limb** (gold standard)

Answer 17

+Risk factors present (“provoked”) Symptoms * Dyspnea, cough, chest pain (pleuritic), hemoptysis, syncope, shock, sudden cardiac arrest Clinical signs * Tachycardia (MOST COMMON), hypoxia (especially with exertion- 6 min walk test), tachypnea, cyanosis, fever, leg swelling (DVT)

Answer 18

1. Obtain history and physical exam 2. Rule out other medical emergencies (ie EKG, troponin level, chest-ray) 3. Calculate Well’s score 4. If appropriate, check D dimer level 5. If elevated D dimer level or high clinical suspicion, confirm with CT angiogram of the chest (if eGFR <60, substitute with V/Q scan)

Answer 19

* Elevated D dimer level * EKG: Normal vs. Sinus tachycardia vs. S1Q3T3 sign * Chest x-ray: Usually normal * Echocardiogram: Normal or signs of RV strain (cor pulmonale)

Answer 20

* Left: Westermark's sign * Right: Hampton's hump

Answer 21

* Anticoagulation is mainstay of therapy * 3 months for distal (smaller vein) DVT * 3-6 months for PE, multi-vessel, or proximal DVT (larger vein)

Answer 22

* Indirect Thrombin inhibitors (heparin, enoxaparin, fondaparinux) * Direct Thrombin Inhibitors (dabigatran) * Direct Factor Xa Inhibitors/DOACs (rivaroxaban, apixaban) * Vitamin K antagonists (warfarin)

Answer 23

Ciraparantag

Answer 24

* Active bleeding * Major trauma * Recent or planned high risk surgery * Severe bleeding disorder (as with liver failure) * Intracranial hemorrhage

Answer 25

* History of recurrent bleeding from multiple gastrointestinal telangiectasias * Intracranial or spinal tumors * Large AAA with concurrent uncontrolled HTN * Stable aortic dissection * Recent or planned low risk surgery * High risk of falling * Platelet count < 50,000 * INR >1.5

Answer 26

* If anticoagulation is contraindicated in patient with VTE, consider an Inferior Vena Cava filter * Prevents emboli to lungs (PE) but causes endovasular injury so can increase risk of DVT but decrease becoming PE * Temporary

Answer 27

* Fibrinolysis (ie IV tissue plasminogen activator) * Pharmaco-mechanical thrombolysis (catheter-directed) * Surgical embolectomy

Answer 28

* **Leiden factor V mutation (MC)** * Anticardiolipin/antinuclear/antiphospholipid * Antithrombin III assay * HIT assay * Prothrombin 20210A mutation antibodies * Protein C assay * Protein S assay * Lupus anticoagulant * Fibrinogen level * Lipid panel * Thyroid Stimulating Hormone * Cocaine metabolites

Answer 29

* Most common inherited thrombophilia disorder * Results from a point mutation in the F5 gene, which encodes the factor V protein in the coagulation cascade * Family history likely present * Leads to protein C resistance (leads to DVT and PEs * Diagnosed by gene testing for mutation (arterial thrombi common)

Answer 30

* May occur concomitantly or alone * PROS or PROC gene mutations * Acquired forms also exists * Diagnosed by combination of quantitative and functional assays

Answer 31

Adhesion, Aggregation/Activation, & Stabilization * Primary hemostasis is when your body forms a temporary plug to seal an injury. To accomplish that, platelets that circulate in your blood stick to the damaged tissue and activate. That activation means they can “recruit” more platelets to form a platelet “plug” to stop blood loss from the damaged area

Answer 32

Coagulation Cascade * Secondary hemostasis refers to the deposition of insoluble fibrin, which is generated by the proteolytic coagulation cascade. This insoluble fibrin forms a mesh that is incorporated into and around the platelet plug. This mesh serves to strengthen and stabilize the blood clot.

Answer 33

More modern view of coagulation: 1. Initiation phase 2. Amplification phase 3. Propagation phase 4. Stabilization

Answer 34

Fibrin clot degradation * Fibrinolysis is the degradation of the fibrin network of a blood clot. Fibrinolysis is required to achieve hemostatic balance. Fibrinolysis can occur naturally in the body or with delivery of pharmacological agents. Rate of fibrinolysis is affected by the fibrin structure and the clot's cellular components.

Answer 35

Signs of primary hemostatic dysfunction (platelet disorder)

Answer 36

Signs of secondary hemostatic dysfunction (clotting factor disorder)

Answer 37

1. CBC 2. “Coags”: * aPTT, partial thromboplastin time, tests intrinsic pathway, normal range: 25-40 sec * PT, prothrombin time, tests extrinsic pathway, normal range 11-15 sec * INR, international normalized ratio, normal value 1.0 +/- 3. Thromboelastogram (TEG)-> surgery setting

Answer 38

* aPTT, partial thromboplastin time, tests intrinsic pathway, normal range: 25-40 sec * PT, prothrombin time, tests extrinsic pathway, normal range 11-15 sec * INR, international normalized ratio, normal value 1.0

Answer 39

TEG is a non-invasive test that quantitatively measures the ability of whole blood to form a clot. The principle of this in vitro test is to **detect and quantify dynamic changes of the viscoelastic properties of a blood sample during clotting under low shear stress.**

Answer 40

Thrombin time, TT/TCT (thrombin clotting time: tests common pathway, along with fibrin split products)

Answer 41

* Occurs within 5-14 days of exposure to unfractionated heparin or, less likely, LMWH * Due to antibodies made against platelet factor 4 (PF4); reduce number and activate platelets * 4 T’s score to assess probability of HIT (Thrombocytopenia, Timing relative to heparin exposure, presence of Thrombosis, and oTher causes for thrombocytopenia) * Confirmed by ELISA or functional assays (takes time so that is why the 4 T were made)

Answer 42

Management: stop heparin & avoid future exposures, venous dopplers of bilateral lower extremities, & start a non-heparin anticoagulant (ie argatroban, fondaparinux) -> because clots

Answer 43

* Autoimmune disorder with IgG antibodies against platelets * Affects both children and adults * Signs/symptoms of thrombocytopenia-> mild bleeding * Laboratory exams: Platelet count <50k (low), no anemia or leukopenia (cells are good) , enlarged platelets on peripheral smear, normal coagulation studies (always check coag). Platelet-associated IgG antibody assay available * Diagnosis of exclusion | F>M, chlidren with viral or adults in 20-50yo

Answer 44

* Required only when platelets <30k or excessive bleeding * First line therapy: Corticosteroids, IVIG, Anti-RhoD or RhoGAM® if Rh+, transfusions if bleeding * Second line therapy: thrombopoietin receptor agonists, rituximab, fostamatinib, splenectomy for relapses

Answer 45

* Microangiopathy due to antibodies to ADAMTS13, pregnancy, malignancy, HIV, drugs (quinine), or infection * HUS may be associated with E. coli O157:H7 or Shiga toxin, especially in children * **Medical emergency due to ischemic multi-organ failure** | LOOKS SICK UNLIKE ITP

Answer 46

* Labs/Diagnostics: low platelet count, normal PT and PTT, elevated creatinine & BUN, hemolysis*, ADAMTS13 assay (indicates TTP over HUS) * Treatments: emergent plasma exchange if TTP >HUS, eculizumab if HUS>TTP, RBC transfusions, hemodialysis, IVIG, corticosteroids, rituximab, cyclophosphamide, splenectomy ## Footnote *low hgb/hct, schistocytes on peripheral smear, elevated reticulocytes, elevated LDH, elevated indirect bilirubin, hemoglobinuria

Answer 47

* Peri-partum disorder (3rd trimester) on eclampsia spectrum (usually increase BP and proteinuria) * Labs: platelet count <100k, AST & ALT elevated more than 2x, bilirubin elevated, RBC fragments on peripheral blood smear, low serum haptoglobin <20, & LDH >600 * Risk of bleeding to mother, including hepatic hemorrhage * Risk of placental abruption

Answer 48

Treatment: Prompt delivery is main goal, IV magnesium sulfate to prevent seizures, anti-hypertensives, blood product transfusions

Answer 49

* Von Williebrand’s Disease * Drug induced * Liver failure * Renal failure (uremic platelet dysfunction) * Cardiac bypass * Inherited GpIb-IX or GpIIB-IIIa defects (ie Glanzmann Thromboasthenia or Bernard-Soulier Syndrome); very rare * Inherited Platelet Storage Pool Disorder

Answer 50

* Deficiency or inhibition of Von Williebrand Factor (vWF)-> platelet adhesion (platelet plug) * Types 1(mc: mild)-4 ranging from mild to severe bleeding disorder * Usually inherited * Family history or personal history of excessive bleeding or platelet transfusions, especially mucocutaneous (mild bleeding) * Acquired form is rare & associated with hypothyroidism, autoimmune diseases, & hematologic malignancies

Answer 51

* Diagnosed with **ristocetin platelet test (plasma vWF activity**)/ RIPA (tests platelet aggregation), quantitative vWF antigen, vWF multimer distribution, & factor VIII activity ELISA assay. **PFA-100 abnormal, especially with types 2A, 2B, 2M, and 3**. * Other labs: Possible prolonged PTT (due to decrease in factor VIII activity) with normal PT & platelet count-> PT, INR normal so PFA

Answer 52

* Hemostatic medications (help you clot): DDAVP-desmopressin, aminocaproic acid, or tranexamic acid(ER) * Replacement therapies: vWF concentrate and/or factor VIII concentrate (If you have major surgery)

Answer 53

NSAIDs, aspirin, & clopidogrel (Plavix®)

Answer 54

* NSAIDs and aspirin inhibit COX-1, which decreases production of thromboxane 2, so platelet aggregation is inhibited * Aspirin & NSAIDs should be avoided in those with active bleeding, thrombocytopenia, or platelet dysfunction(VWD+Precedure) * Also avoid in preoperative period (stop 7-30days) & if already on anticoagulants or SSRIs (GI bleeding)

Answer 55

* PT prolonged, PTT normal: Factor VII * PT normal, PTT prolonged: Factors VIII, IX, XI, XII * Both PT & PTT prolonged: Factors V, X

Answer 56

* DIC * Liver Disease * Vitamin K Deficiency * Acquired inhibitors of coagulation

Answer 57

* Hemophilia A * Hemophilia B * Von Williebrand’s Disease (factor VIII affected)

Answer 58

* X -linked recessive clotting factor deficiency * Type A is factor 8 deficiency, type B is factor 9 deficiency (christmas) * Signs/symptoms: severe bleeding, spontaneous hemarthroses, muscle hematomas, GI bleeding, bleeding with **circumcision procedure(first clue)** * Labs: Prolonged PTT with normal PT; Factor 8 or 9 assay is diagnostic. Mixing study required to rule out clotting factor inhibitors.

Answer 59

Treatment/Management: factor infusions, DDAVP, aminocaproic or tranexamic acid, avoid blood thinners (include OTC), avoid trauma/contact sports if severe

Answer 60

* Dietary vitamin K1(greens), K2(GI flora)/ phylloquinone found in green vegetables like spinach * Most often due to malnutrition, fat malabsorption (ie Celiac’s), or Warfarin * Signs/symptoms: range from superficial bleeding (mild if early on) & easy bruisability to severe bleeds

Answer 61

* Labs: PT prolonged to >4 times normal limit, PTT also prolonged if severe * Treatment/Management: Treat underlying cause. Corrects with administration of supplemental Vitamin K (PO, IM, SubQ, IV). PO preferred if non-emergent bleeding ## Footnote IV: risk with allergy

Answer 62

* Fibrinogen, prothrombin, & most numbered factors are synthesized in the liver * Labs: PT>>PTT prolonged, INR>1.5, prolonged TT, possibly low platelet count * Consider factor assays; factor V deficiency indicates liver failure over vitamin K deficiency ## Footnote Decrease platelets dt liver making thrombintin and no coag factors

Answer 63

Treatment: Administer fresh frozen plasma transfusion if bleeding * has coag factors

Answer 64

* Syndrome of widespread, acute, inappropriate triggering of 1° and 2 ° hemostasis * Coagulation factors, fibrinogen & platelets overstimulated followed by rapid depletion * Results in micro-occlusion of vessels resulting in organ failure & uncontrolled bleeding * Medical emergency

Answer 65

Signs/symptoms: purpura, oozing from venipuncture sites, bleeding mucosal surfaces, gangrene, superficial thrombophlebitis, digital ischemia, severe hemorrhage of GI tract, respiratory distress, MI, CVA, seizures, hepatic failure, renal failure, shock

Answer 66

* Labs: Prolonged PT and PTT, platelet count <100k (by the time of labs, in depletion phase), **low fibrinogen** (clotting factor), elevated D-dimer, elevated fibrin split products, peripheral blood smear with schistocytes * Treatment/management: correct underlying cause, FFP or cryoprecipitate transfusion, platelet transfusion if bleeding predominates, tissue plasminogen activator (TPA) or low-dose heaprin if clots predominate

Answer 67

* Auto-antibodies against a specific coagulation factor * Suspect when clotting factor deficiency does not correct as expected * High incidence with hemophilia * Also associated with autoimmune disease (Autoantibodies), solid tumor cancers, and post-partum | SEREVE BLEEDING

Answer 68

* Labs: Abnormal PT and/or PTT/INR * 1:1 mixing study does not correct * Most common is anti-factor VIII * Treatment: Recombinant clotting factor when bleeding, steroids, cyclophosphamide, rituximab, emicizumab

Answer 69

A reduction below normal in one or more of the following: 1. Hemoglobin (Hgb) 2. Hematocrit (Hct)-> 3 times hgb 3. RBC Count Identified via complete blood count

Answer 70

* Iron deficiency * Folic acid deficiency * Vitamin B12 deficiency * Anemia of chronic disease * Hypothyroidism/-gonadism * Bone marrow suppression or failure (malignancy, medications, aplastic anemia) | CHI AF

Answer 71

* Sickle cell anemia * Thalassemias * Sideroblastic * Methoglobinemia

Answer 72

Hemolysis -Autoimmune -G6PD deficiency -PNH -TTP/HUS -Infections -Thalassemias and sickle cell -Hypersplenism

Answer 73

* Target cells- thalassemia, liver disease, hemoglobin C * Burr cell- liver disease, renal disease * Tear drop cell- myelofibrosis * Schistocytes- microangiopathic hemolytic anemia

Answer 74

* Howell jolly bodies- splenectomy * Basophilic stippling- lead poisoning * Acanthocytes- liver disease * Elliptocytes- iron deficiency, thalassemia

Answer 75

* Stomacytes- alcoholic liver disease * Sickle cells- sickle cell disease * Rouleaux formation- multiple myeloma * Sideroblasts- myelodysplastic syndrome

Answer 76

* Constitutional: **fatigue** (likely if Hgb <10), dizziness, general weakness, reduced exercise capacity * Cardiovascular: tachycardia, palpitations, systolic murmur, hypotension if due to acute bleeding, angina if severe * Respiratory: **dyspnea**, tachypnea * Integumentary: reduced perfusion- delayed capillary refill, **pallor of skin**, **oral mucosa, & conjunctiva**, cold & brittle nails

Answer 77

* Renal: reduced perfusion, proteinuria, fluid retention * Gastrointestinal: indigestion * Neurological: cognitive function, mood, vertigo * GU: menstrual disturbances, loss of libido, impotence

Answer 78

* Due to negative iron balance (not enough) * Foods rich in Fe include meat, fish, eggs, leafy greens, & beans (animal and plants) * **Most often due to bleeding!** Suspect it’s a secondary disorder in young children, adult men, and post-menopausal women * Second most common underlying disease is a malabsorption disorder

Answer 79

Signs/symptoms: pica (ie ice), koilonychia “spoon nails”, cheilosis, dysphasia (Plummer Vinson Syndrome), or CNS symptoms if severe

Answer 80

Decrease iron-> hypochronic

Answer 81

Signs/symptoms: glossitis-smooth, **beefy red tongue, paresthesias, peripheral neuropathy**, impaired proprioception and/or vibratory sense, balance difficulty, psychosis or dementia possible, anorexia, weight loss, diarrhea

Answer 82

* Folic acid is normally ingested, absorbed in jejunum, circulates unbound as 5-methyl-THF, & requires B12 to enter the cells * Found in green leafy vegetables, liver, fruits, & nuts * Patients at risk: **malnutrition (alcoholics, elderly)**, dietary deficiency, tropical sprue, medication effect (ie Bactrim, phenytoin, methotrexate), pregnancy (increase demand so prenatal vit needed), loss due to hemodialysis

Answer 83

* Labs: Macrocytic & normochromic anemia, high RDW, & low serum & RBC folate levels * Treatment: Oral Folic acid 1-5, but up to 15mg daily for 2-4 months

Answer 84

* Disorders of ineffective erythropoiesis; iron not correctly incorporated into RBC * Examples: myelodysplastic syndrome, lead poisoning, Vit B6 deficiency, Cu deficiency, alcoholism, drugs (ie isoniazid), hereditary * Labs: may be microcytic (ie hereditary) or macrocytic (ie alcoholism & MDS)

Answer 85

* Diagnostics: **ringed sideroblasts** on bone marrow biopsy * May lead to hemochromatosis * Treatment: treat underlying cause (ie pyridoxine)

Answer 86

* Caused by increase in proinflammatory cytokines which decrease erythropoiesis * Associated with chronic infection (TB, chronic UTI), autoimmune diseases (ie SLE, RA), malignancies, liver disease, alcoholism*, hypo- or hyperthyroidism | *Usually macrocytic

Answer 87

* Labs: Normocytic or **microcytic**, normochromic anemia. Ferritin level elevated in response to inflammation. (look at iron levels, then ferritin level) * Treatment: Address the underlying cause. May support with RBC transfusions and exogenous EPO. (IL-1 can lower EPO)

Answer 88

* Bone marrow failure resulting from damage to hematopoietic stem cells * Presents as profound anemia plus leukopenia plus thrombocytopenia (low of all counts) * Diagnosed via bone marrow biopsy * 65% of cases are idiopathic * Other cases due to SLE, chemotherapy, toxins (benzene), drugs (ie phenytoin, NSAIDs), viruses (EBV), radiation poisoning, Fanconi anemia

Answer 89

Treatments: transfusions, anti-thymocyte globulin, cyclosporine, cyclophosphamide, allogeneic bone marrow transplant

Answer 90

High: * Elevated reticulocyte count and/or reticulocyte production index * Elevated unconjugated/indirect bilirubin level * Elevated lactate dehydrogenase (LDH) Low * Low hemoglobin with high MCV and high RDW -> macrocytic anemia * Low haptoglobin level peripheral blood smear * RBC fragments, ie schistocytes Urinalysis with hemoglobinuria Direct Coombs/Antiglobulin Test

Answer 91

* If positive, autoimmune, drug related, transfusion, infection, or cancer. * If negative, G6PD deficiency, PNH, TTP/HUS, or DIC.

Answer 92

* Membrane defects: PNH, hereditary spherocytosis, hereditary * elliptocytosis * Glycolytic defects: pyruvate kinase deficiency * Oxidation vulnerability: G6PD deficiency * Hemoglobinopathies: sickle cell * Vigorous exercise

Answer 93

* Inherited & rare * Abnormal sensitivity of RBCs to lysis by complement, especially at night * Results from somatic mutation in the PIG-A gene * Signs/symptoms: Episodic hemoglobinuria (reddish brown) in a child, most often with first micturition in the morning

Answer 94

* Disorders of globin synthesis or stability; lead to anemia * Most are inherited * Peri-partum screening is common * Types: Thalessemias, Sickle Cell Disorder, & others

Answer 95

* Hemoglobin= heme + 4 globin units (2 alpha chain genes and 2 beta) * Heme= iron + 4 protoporphyrins

Answer 96

from asymptomatic carrier status to severe anemia with extramedullary hematopoiesis, skeletal changes, hepatosplenomegaly, & hemochromatosis

Lecture 1 (hem/onc)-Exam 1 Flashcards

(202 cards)