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Flashcards in Heme Deck (169):

Heinz bodies (inclusions within red blood cells composed of denatured hemoglobin)

G6PD deficiency, Alpha-thalassemia


Spherocytes (Due to underlying pathology, blood cell contracts to its most surface-tension efficient and least flexible configuration, a sphere)

Hereditary spherocytosis and autoimmune hemolytic anemia



Very often seen in Iron deficiency (also could be seen in Thalassemia, Myelophthisic anemias, and Megaloblastic anemias)


Target Cells (seen on a peripheral blood smear when there is excess membrane relative to the amount of hemoglobin)

Membrane may be excessive in liver disease. Intracellular hemoglobin may be lowered during iron deficiency, thalassemia, hemoglobin C or SC and other hemoglobinopathies.


Teardrop Cells/dacrocytes (a type of poikilocyte that is shaped like a teardrop)

Myelofibrosis and myelophthisic anemia


Schistocytes (fragmented parts of red blood cells)

Microangiopathic Hemolytic Anemia


Bite Cells (result from the removal of denatured hemoglobin by macrophages in the spleen)

G6PDH deficiency


Echinocytes (red blood cells that have a spiked cell membrane, due to abnormal thorny projections)

Can be due to an osmotic abnormality in liver disease, kidney disease


Howell-Jolly bodies (Nuclear remnants)



Basophilic stippling (Clumped ribosomes in RBCs that are more severe than in reticulocytes, and can be seen without special stain)

Lead poisoning (coarse stippling) and Thalassemia. Not seen in Iron deficiency


Pappenheimer bodies (iron granules in RBCs)

Non specific finding that could be seen in Sideroblastic anemia, hemolytic anemia, and sickle cell disease


Hemoglobin C crystals

Homozygous hemoglobin C


Cytokine receptor tyrosine kinase, expressed on the surface of many hematopoietic progenitor cells, that binds ligand on the outside of the cell. Activating mutations in what are found in 41% of AML



A receptor tyrosine kinase for stem cell factor that binds ligand on the outside of the cell. Activating mutations in what are found in certain AML subtypes ("core binding factor leukemias), systemic mastocytosis, and GI stromal tumors (inhibited by imatinib)



A family of cell surface receptors that function in cell fate determination during embryogenesis in multiple tissues that is frequently mutated in T cell ALL



Recognizes ligands such as jagged, delta, and delta-like on adjacent cells.



Signaling involves proteolysis by gamma-secretase and translocation to the nucleus. Signaling promotes pluripotent stem cell survival, specifies lymphoid lineage over myeloid differentiation, and specifies T cell over B cell lineage in common lymphoid progenitors



Mutations of what are found in more than 50% of human T cell lymphoblastic leukemia



What normally degrades hypoxia-inducible factor (HIF) but stops degrading it in hypoxic conditions.

Von Hippel Lindau


Hypoxia-inducible factor (HIF) activates what

Erythropoietin (EPO)


EPO binds which receptor

JAK receptor


JAK phosphorylates



What does STAT do

Activates transcription


What is often deleted in renal clear cell carcinomas and what is the consequence

Von Hippel-Lindau protein is deleted. Without VHL, HIF will not be degraded and will be free to activate erythropoiesis. Therefore, some patients with renal cell carcinomas develop secondary polycythemia (the proportion of blood volume that is occupied by red blood cells increases)


Automated blood analysis of Hb

lyse cells, measure spectrophotometrically. The more hemoglobin, the less light passes through


Cell counting is done by

Flow cytometry


In hydrodynamic focusing, cells line up in mid stream and light scatter or electrical impedance is measured. What do forward and side scatter indicate

Forward scatter is a measure of size, side scatter is a measure of internal complexity


A family of single-pass transmembrane proteins that show expression on early hematopoietic and vascular-associated tissue



CD34+, multipotent, self-renewing cells

Pluripotent hematopoietic stem cells


CD34+, partially differentiated/usually unipotent cell (has lost most or all of the stem cell multipotency)

Blast cell


Quiescent, non-dividng state of pluripotent hematopoietic stem cells is reflected by the expression of

cyclin-dependent kinase inhibitors


Definitive hematopoiesis produces

Smaller cells that express only adult hemoglobins


4/5 of CSF receptors signal through

JAK/STAT pathway


Produced by renal interstitial cells in response to hypoxia by hypoxia inducible factor (HIF)

Erythropoietin (EPO)


Prevents apoptosis of erythroid progenitors

Erythropoietin (EPO)


Mutation in a cytoplasmic (non-receptor) tyrosine kinase, JAK-2, which transduces the EPO signal, is found in almost all cases of

Polycythemia vera


Produces hypochlorite from peroxide, and is the most specific marker of myeloid differentiation (as apposed to lymphoid or erythroid)



Measure of the average red blood cell size

Mean corpuscular volume (MCV)


Measure of the concentration of hemoglobin in a given volume of packed red blood cells

Mean corpuscular hemoglobin concentration (MCHC)


Variability in RBC size

RBC distribution width (RDW)


Increase in abnormal red blood cells of any shape where they make up 10% or more of the total population



Heme is turned into unconjugated bilirubin where

In the reticuloendothelial cells of the spleen


Not soluble in water, due to intramolecular hydrogen bonding. It is then bound to albumin and sent to the liver.

Unconjugated bilirubin


Bilirubin is conjugated with what, making it soluble in water

Glucuronic acid


What binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity



The haptoglobin-hemoglobin complex will then be removed by

The reticuloendothelial system (mostly the spleen)


What is abundant in red blood cells and can function as a marker for hemolysis

Lactate dehydrogenase (LDH)


In clinical settings, what is used to screen for and monitor intravascular hemolytic anemia

The haptoglobulin assay (In intravascular hemolysis, free hemoglobin will be released into circulation and hence haptoglobin will bind the Hb)


Inclusions within red blood cells composed of denatured hemoglobin. They are formed by damage to the hemoglobin component molecules, usually through oxidant damage, or from an inherited mutation

Heinz bodies


The presence in the blood of erythrocytes of varying sizes and abnormal shapes




DAF: regulates the complement system on the cell surface



MIRL: inhibits the complement membrane attack complex


Indirect Coombs test

Used to detect in-vitro antibody-antigen reactions. It is used to detect very low concentrations of antibodies present in a patient's plasma/serum prior to a blood transfusion. In antenatal care, the IAT is used to screen pregnant women for antibodies that may cause hemolytic disease of the newborn. The IAT can also be used for compatibility testing, antibody identification, RBC phenotyping, and titration studies


Direct Coombs test

Used to detect if antibodies or complement system factors have bound to RBC surface antigens in vivo


Diagnosis of autoimmune and some forms of drug-induced hemolytic anemia. Evalutation of hemolytic transfusion reactions. Diagnosis of hemolytic disease of newborn.

Direct Coombs test (Direct antiglobulin test)


Detection of incomplete (noncoaggulatinating) antibodies in patient with hemolytic anemia or in patient's serum to potential donor RBCs (or to screening cells. Determination of RBC phenotype using known anti-sera to specific blood group antigens. Titration of allo-anti-D in Rh-negative pregnant women

Indirect Coombs test (Indirect antiglobulin test)


Packed RBCs

Usual component for RBC therapy that is prepared by centrifugation of the WB donation which removes most of the plasma. It is stored at 4 degrees C (storage life is 35 days).


Fresh Frozen Plasma

After removal of the RBC fraction of the whole blood donation, the platelet-rich plasma then subjected to a "hard" centrifugation to remove the platelets and most WBCs to form "platelet-poor" plasma.


Random donor and single donor platelets

Whole blood donation (random donor) or apheresis (single donor). Platelets stored at 22-24 degrees C (storage life is 5 days).



Cryoprecipitated Antihaemophilic Factor: The cold-precipitated concentration of Factor VIII (the 'antihemophilic factor" AHF). Just prior to transfusion, CRYO is quick-thawed at 37 degrees C and is pooled with other units. Storage of 12 months in frozen state, 6 hr once thawed, and 4 hours once pooled



A process by which whole blood is removed from the donor by a closed-system instrument which houses a centrifuge that separates the blood components, selectively removes the desired component, and then recombines the remaining components for return to the donor


Occurs very soon after transfusion of incompatible RBCs

IHTR - immediate hemolytic transfusion reaction


Antibodies causing IHTRs bind complement to the RBC surface and have efficient in vitro lytic properties. RBC destruction occur primarily by intravascular hemolysis. The 4 most commonly identified RBC antibodies causing IHTRs are

Antio-A, Anti-kell, Anti-kidd a, and anti-duffy a


Signs and symptoms: IHTR

Fever with/without chills, oliguria, DIC or coagulopathy, hypotension


The majority of IHTRs are caused by

Clerical error, they are potentially preventable


Noncardiogenic pulmonary edema reactions associated with transfusion. Recent sweeping changes that could affect 10-20% of female donors

TRALI - transfusion related acute lung injury


Signs and symptoms: TRALI

Chills, cough, fever, cyanosis, hypotension, and increasing respiratory distress shortly after transfusion.


Least common AIHA, more common in children than other types in association with viral illnesses, dramatic clinical presentation: acute paroxysmal or intermittent episodes of hemoglobinuria upon exposure to cold.

Paroxysmal cold hemoglobinuria


What antibody screen and crossmatch is needed before transfusion



A blood transfusion condition that occurs due to a rapid transfusion of a large volume of blood.

TACO - transfusion related circulatory overload


The primary symptoms of TACO are

Dyspnea, orthopnea, peripheral edema, and rapid increase of blood pressure


TACO differs from Transfusion related acute lung injury (TRALI)

By having longer hospital stays and increased morbidity


TA-GVHD - transfusion-associated graft versus host disease can develop how many days after the transfusion

4-30 days


a rare complication of blood transfusion, in which the donor T lymphocytes mount an immune response against the recipient's lymphoid tissue

TA-GVHD - transfusion-associated graft versus host disease


Typical symptoms: TA-GVHD - transfusion-associated graft versus host disease

Fever, erythematous maculopapular rash (which can progress to generalised erythroderma), toxic epidermal necrolysis in extreme cases, cough, abdominal pain, vomiting, and profuse diarrhea


a biochemical technique used to detect a virus or a bacterium. These tests were developed to shorten the window period, a time between when a patient has been infected and when they show up as positive by antibody tests

NAT -nucleic acid testing


Most common cause of transfusion-associated fatalities (usually a clerical error resulting in a recipient receiving the wrong blood type)

AHTR - acute hemolytic transfusion reaction


Occurs about 3-7 days after transfusion. An anamnestic response from previous sensitization from previous pregnancy, transfusion or transplant. Antibody not detected in routine pretransfusion testing. RBC destruction occurs primarily by extravascular hemolysis.

DHTR - delayed hemolytic transfusion reaction


Signs and symptoms: DHTR - delayed hemolytic transfusion reaction

Milder compared to IHTR and is commonly subclinical (usually mild fever or fever with chills and/or mild to moderate jaundice). Only treatment for asymptomatic anemia: monitor patient to reduce risk of renal failure.


Immediate or delayed. Most often occur with transfusion of ABO-incompatible RBCs (AB-incompatible plasma-containing products or chemical/physical injury). May be stimulated by a number of diseases

Acute and delayed HTRs


One of the most common transfusion reactions. 1 degree C (2 degrees F) rise in temperature associated during or shortly after transfusion and having no other explanation

Febrile nonhemolytic transfusion reactions (FNHTR).


Signs and symptoms: Febrile nonhemolytic transfusion reactions (FNHTR).

Fever with chills and hypotension (usually mild), severe reactions can rarely occur and mimic sepsis.


One of the most common transfusion reactions. Appear within minutes of transfusion and represent mild immediate hypersensitivity type immune reactions to plasma proteins

Allergic reaction


Moderate to severe immediate hypersensitivity type immune reactions. Two significant features distinguish these reactions from other types of transfusion reactions: Fever is absent, and signs/symptoms occur after transfusion of just a few mls of plasma or plasma-containing component

Anaphylactic reaction


A type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation. Usually less severe

Anaphylactoid reaction


Majority are mild, most reported as FNHTR. Local erythema, prusitis, hives. Can rarely be more severe.

Allergic reaction


Coughing, dyspnea, nausea, vomiting, bronchospasm, chest pain, hypotension, diarrhea, and shock. Occurs in IgA-deficient patients who have class-specific anti-IgA. IgA deficiency is relatively common but the incidence of this is low

Anaphylactic reaction


Urticaria, periorbital edema, dyspnea, and laryngeal edema. Occurs in patients with decreased or normal levels of IgA with a limited type-specific anti-IgA antibody that reacts with the light chain fragment of the donor's IgA.

Anaphylactoid reaction


The single most important transfusion-transmitted infection



Methylmalonyc CoA mutase requires B12 but not folate and catalyzes what reaction

Methylmalonyl CoA to succinyl CoA


Serum folate reflects recent folate (may be normal in deficient patient who has had recent intake). What is a better reflection of tissue folate levels.

Red cell folate


What refers to the presence of nucleated red blood cells and primitive white blood cells. It is seen in bone marrow failure, myelofibrosis and extramedullary haemopoiesis.

Leukoerthyroblastic change


Measures of the extrinsic pathway of coagulation

Prothrombin time (PT)


PT measures which factors

I (fibrinogen), II (thrombin), V, VII, and X.


Used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status.

Prothrombin time (PT)


Performance indicator measuring the efficacy of both the "intrinsic" (now referred to as the contact activation pathway) and the common coagulation pathways.

Activated partial thromboplastin time (APTT). Also called PTT


Apart from detecting abnormalities in blood clotting, it is also used to monitor the treatment effects with heparin, a major anticoagulant.

Activated partial thromboplastin time (APTT). Also called PTT


PTT measures which factors

I, II, V, VIII, IX, X, XI, & XII (Notably, deficiencies in factors VII or XIII will not be detected with the PTT test)


Heparin-induced thrombocytopenia (HIT) is caused by

The formation of abnormal antibodies that activate platelets.


The receptor for von Willebrand factor that is important in clot formation.

glycoprotein Ib (GpIb)


A rare autosomal recessive coagulopathy (bleeding disorder) that causes a deficiency of glycoprotein Ib (GpIb)

Bernard-Soulier syndrome


Glycoprotein IIb/IIIa (GpIIb/IIIa) is a receptor for what



An abnormality of platelets. It is an extremely rare coagulopathy (bleeding disorder due to a blood abnormality), in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), resulting in no fibrin/fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.

Glanzmann's thrombasthenia


An ex vivo assay for live platelet function. Exogenous antibiotic is added in a graded fashion to aggregate platelets with help of von Willebrand factor (vWF). It is used to diagnose von Willebrand disease (vWD).

Ristocetin aggregation test


An inherited deficiency in clotting factor VIII, which causes increased bleeding and usually affects males.

Hemophilia A


Inheritance of Hemophilia A

X-linked recessive trait, and thus occurs in males and in homozygous females


A blood clotting disorder caused by a mutation of the Factor IX gene, leading to a deficiency of Factor IX

Hemophilia B (the second most common form of hemophilia)


Inheritance of Hemophilia B

It is an X-linked recessive trait (The factor IX gene is located on the X chromosome). It can arise de novo without a family history


A pathological activation of coagulation (blood clotting) mechanisms that happens in response to a variety of diseases. It leads to the formation of small blood clots inside the blood vessels throughout the body. As the small clots consume coagulation proteins and platelets, normal coagulation is disrupted and abnormal bleeding occurs

Disseminated intravascular coagulation (DIC)


What effect does DIC have on organs in the body

The small clots disrupt normal blood flow to organs (such as the kidneys), which may malfunction as a result.


a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf). It is secreted in blood and degrades large vWf multimers, decreasing their activity



A disease characterized by hemolytic anemia (anemia caused by destruction of red blood cells), acute kidney failure (uremia), and a low platelet count (thrombocytopenia). It predominantly, but not exclusively, affects children. Most cases are preceded by an episode of infectious, sometimes bloody, diarrhea caused by E. coli O157:H7, which is acquired as a foodborne illness or from a contaminated water supply.

Hemolytic uremic syndrome (HUS)


The condition of having an abnormally low platelet count (thrombocytopenia) of unknown cause (idiopathic). Most incidents appear to be related to the production of antibodies against platelets.

Idiopathic/Immune thrombocytopenic purpura (ITP)


A rare disorder of the blood-coagulation system, causing extensive microscopic clots to form in the small blood vessels throughout the body. These small blood clots, can damage many organs including the kidneys, heart and brain. In the era before effective treatment with plasma exchange, the fatality rate was about 90%

Thrombotic thrombocytopenic purpura (TTP)


Diagnose: PT = high, PTT = high, bleeding time = high, platelets = low

Liver Failure or DIC


Diagnose: PT = high, PTT = normal or high, bleeding time = normal, platelets = normal

Vit K Deficiency


Diagnose: PT = normal, PTT = high, bleeding time = high, platelets = normal

VWF Disease


Diagnose: PT = normal, PTT = high, bleeding time = normal, platelets = normal

Hemophilia A & B


Presentation: Acute Idiopathic/Immune thrombocytopenic purpura (ITP)

Disorder of childhood with equal distribution between both sexes. Onset is abrupt and may be preceded by a viral illness. Usually resolves spontaneously within 6 months. May progress to chronic ITP in about 20% of cases.


Presentation: Chronic Idiopathic/Immune thrombocytopenic purpura (ITP)

More common than acute. Presentation: usually women <40 with mucocutaneous bleeding, epistaxis, menorrhagia, and petechiae


IgGs against GPIIb-IIIa and GPIb-IX. Opsonized platelets destroyed by cells of mononuclear phagocyte system (spleen). Suppression of megakaryocyte proliferation and maturation, although these are usually present in approximately normal numbers. Cytotoxic T cells may also play a role. Generalized defect in immune regulation (too few regulatory T cells and B cells)

Chronic Idiopathic/Immune thrombocytopenic purpura (ITP)


Occurs in 5% of patients receiving heparin

Heparin-induced thrombocytopenia


Occurs rapidly after beginning heparin therapy and is clinically not significant.

Type I Heparin-induced thrombocytopenia


Occurs 5-14 days after beginning heparin therapy.

Type II - Heparin-Induced Thrombocytopenia/ Thrombosis Syndrome (HITTS).


Antibodies directed against complex of heparin and platelet factor 4 (PF4). Heparin binding exposes a neoepitope on PF4, which forms a tetramer on the platelet membrane. Immune complexes on the platelet surface cause platelet activation by binding the activating low affinity receptor for IgG

Type II - Heparin-Induced Thrombocytopenia/ Thrombosis Syndrome (HITTS).


Pentad of symptoms common to syndromes of thrombotic microangiopathies

Fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neurologic deficits, and renal failure.


Usually presents in adults and neurologic symptoms are common. It usually occurs due to acquired antibodies to ADAMTS13 causing spontaneous aggregation of platelets by large VWF multimers. Can also be due to hereditary defect

Thrombotic thrombocytopenic purpura (TTP)


Usually presents in children. It may occur with an infectious gastroenteritis with bloody diarrhea. Renal symptoms dominate, but neurologic symptoms are less common. Caused by direct damage to endothelium due to E. coli O157:H7 toxin related to shiga toxin.

Hemolytic uremic syndrome (HUS)


Associated with inherited deficiency of inhibitors of the alternative complement pathway. Endothelial damage due to complement activation leads to microvascular thrombosis

Atypical Hemolytic uremic syndrome (HUS)


Direct infection of megakaryocytes by HIV. CD4 and CXCR4 receptors for HIV are present on megakaryocytes. Antibodies against HIV gp120 antibodies cross react with GPIIbIIIa cause secondary ITP

HIV associated thrombocytopenia


Most common blood component associated with bacterial contamination



Administering what will cause von Willebrand factor to bind the platelet receptor glycoprotein Ib (GpIb)

The antibiotic ristocetin


What happens when ristocetin is added to normal blood

It causes agglutination


Where does Von Willebrand factor come from

The majority comes from the endothelial cell (Weibel–Palade bodies are the storage granules of endothelial cells. They store and release two principal molecules, von Willebrand factor and P-selectin.) but some comes from the platelet itself.


What is the role of ADP in hemostasis

ADP induces the expression of GpIIb/IIIa receptors on the surface of the platelet


What is the clinical presentation of a primary hemostasis problem

Mucosal (epistaxis, hemoptysis, GI bleeding, hematuria, and menorrhagia) and skin bleeding (petechia*, purpura, ecchymoses, and easy bruising). Intracranial bleeding occurs with severe thrombocytopenia. *Petechia are a sign of thrombocytopenia and are not usually seen with qualitative disorders


Name this disorder: Splenic plasma cell production of autoimmune IgG against platelet antigens (GpIIb/IIIa). Platelets bound by this autoimmune IgG get consumed by macrophages in the spleen

Immune thrombocytopenic Purpura (ITP)


What is the most common cause of thrombocytopenia in children and adults

Immune thrombocytopenic Purpura (ITP)


What is the clinical presentation of Acute Immune thrombocytopenic Purpura (ITP)

It occurs in children, weeks after a viral infection or immunization. It is self-limited, usually resolving within weeks of presentation. PT/PTT are normal. Platelet count is low (<50k/ul), Increased megakaryocytes on bone marrow biopsy


What is the clinical presentation of Chronic Immune thrombocytopenic Purpura (ITP)

Usualy arises in women of child bearing age. It may be primary or secondary (SLE) and may cause short-lived thrombocytopenia in offspring (anti-platelet IgG can cross the placenta). PT/PTT are normal. Platelet count is low (<50k/ul), Increased megakaryocytes on bone marrow biopsy


Why would splenectomy (only performed in refractory cases) be used to treat Immune thrombocytopenic Purpura (ITP)

It eliminates the primary source of antibody and the site of destruction


What is the cause of Thrombotic Thrombocytopenic Purpura (TTP)

Decreased ADAMSTS13 (autoantibody against it or genetic mutation in ADAMSTS13 gene) which normally cleaves multimers of Von Willebrand Factor for eventual degradation. Large uncleaved multimers lead to abnormal platelet adhesion, resulting in microthrombi


What are the clinical features of TTP and HUS

  1. Skin and mucosal bleeding
  2. Microangiopathic hemolytic anemia
  3. Fever
  4. Renal insufficiency
  5. CNS abnormalities


What are the laboratory findings in TTP and HUS

  1. Thrombocytopenia with increased bleeding time
  2. Normal PT/PTT
  3. Anemia with schistocytes
  4. Increased megakaryocytes


What is Bernard-Soulier Syndrome

A genetic GpIb deficiency That causes impaired platelet adhesion. The blood smear shows mild thrombocytopenia with enlarged (more immature) platelets


What is Glanzmann Thrombasthenia

A genetic deficiency of GpIIb/IIIa causing impaired platelet aggregation


What effect does aspirin have on platelets

It irreversibly inactivates cyclooxygenase causing a lack of TXA2 impairing platelet aggregation


What effect does uremia have on platelet function

Uremia disrupts both platelet adhesion and aggregation


What is the clinical presentation of a secondary hemostasis problem

Deep tissue bleeding into muscles and joints and rebleeding after surgical procedures


What activates the intrinsic and extrinsic pathways of coagulation

Intrinsic (PTT) = Subendothelial Collagen

Extrinsic (PT) = Tissue Thromboplastin


What is the clinical presentation of Hemophilia A

  1. Presents with deep tissue, joint, and post surgical bleeding (depending on severity of deficiency)
  2. Elevated PTT (this will be corrected in a mixing study when normal plasma is added to patient plasma)
  3. Normal PT
  4. Decreased Factor 8
  5. Normal platelet count and bleeding time


What is the clinical presentation of Hemophilia B

1.Presents with deep tissue, joint, and post surgical bleeding (depending on severity of deficiency)
2.Elevated PTT
3.Normal PT
4.Decreased Factor 9
5.Normal platelet count and bleeding time


How can you determine if there is a coagulation factor deficiency or an autoantibody to that coagulation factor

Mixing study: Add normal plasma to patient plasma. If it corrects the aberrant PT/PTT then it is a coagulation factor deficiency. No correction = autoantibody


What is the most common inherited coagulation factor disorder

Von Willebrand Disease (usually autosomal dominant mutation leading to decreased vWF levels) 


What is the clinical presentation of Von Willebrand Disease

  1. It presents with mild mucosal and skin bleeding
  2. Increased bleeding time
  3. Increased PTT (vWF stabilizes Factor 8) but not enough secondary hemostasis impairment to create symptoms
  4. Normal PT
  5. Abnormal ristocetin test (no aggregation of platelets with addition of ristocetin)


What is the treatment for Von Willebrand Disease

Desmopressin: Increases vWF release from Weibel-Palade bodies of endothelial cells


What effect does liver failure have on hemostasis

  1. Decreased production of coagulation factors
  2. Decreased activation of vitamin K by epoxide reductase (present in the liver)
  3. Effect of liver failure is followed using PT


What does Heparin associate with on the surface of platelets to cause Heparin-induced Thrombocytopenia (HIT)

Platelet Factor 4 (antibodies form against the heparin-platelet factor 4 complex and destroys platelets. Fragments of destroyed platelets may activate remaining platelets - leading to thrombosis)


What are the laboratory findings in Disseminated Intravascular Coagulation (DIC)

  1. Decreased Platelet count
  2. Increased PT/PTT
  3. Decreased fibrinogen
  4. Microangiopathic hemolytic anemia
  5. Elevated fibrin split products (D-Dimer)


What activates and inactivates plasmin

  1. Tissue Plasminogen Activator (tPA) activates plasmin
  2. Alpha2-antiplasmin inactivates plasmin


Overactive fibrinolysis presents like DIC but can be differentiated how, and how is it treated

  1. Increased PT/PTT (plasmin destorys coagulation factors) - same as DIC
  2. Increased bleeding time with normal platelet count (plasmin blocks platelet aggregation) - same as DIC
  3. Increased fibrinogen split products without D-Dimers (serum fibrinogen is lysed, however, D-dimers are not formed because fibrin thrombi are absent)
  4. Treated with aminocaproic acid - blocks the activation of plasminogen


What would you see in a pre-mortem thrombus that you would not see in a post-mortem thrombus

  1. Lines of Zahn (alternating layers of blood cells and fibrin)
  2. Attachment to vessel wall


What are the 3 major risk factors for thrombosis

  1. Disruption of blood flow (stasis: immobilization, cardiac wall dysfunction , aneurysm)
  2. Endothelial cell damage (atherosclerosis, vasculitis, high levels of homocysteine)
  3. Hypercoagulable state


Besides the deep veins of the leg, where else does a DVT occur

Hepatic and cerebral veins


What do Protein C and Protein S do

  1. Protein S is a cofactor for Protein C
  2. Deficiency in Protein C and Protein S causes a hypercoagulable state
  3. They decrease negative feedback on the coagulation cascade
  4. They normally inactivate factors V and VIII
  5. Increased risk for warfarin skin necrosis (warfarin inhibits Protein C and Protein S)


What is Factor V Leiden

  1. Mutated form of Factor V that lacks cleavage site for deactivation by proteins C and S
  2. Most common inherited cause of hypercoagulable state


What is Prothrombin 20210A

  1. Inherited point mutation in prothrombin
  2. Results in increased gene expression
  3. Promotes thrombus formation


What is anti-Thrombin III deficiency

  1. Decreases protective effect of heparin-like molecules produced by the endothelium, increasing the risk for thrombus
  2. PTT does not rise with standard heparin dosing (because heparin works by activating anti-thrombin III, which is deficient)
  3. High doses of heparin activate limited ATIII; coumadin is then given to maintain anticoagulated state


Why are oral contraceptives associated with a hypercoagulable state

  1. Estrogen induces increased production of coagulation factors
  2. Increases the risk of thrombosis