Hemostasis and related disorders Flashcards Preview

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Flashcards in Hemostasis and related disorders Deck (41)
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Describe primary hemostasis

- vWB factor (released from Weibel-Palade bodies of endothelial cells and alpa-granules of platelets) binds to exposed collagen.
- GP1b receptor of platelets binds vWF inducing degranulation
- ADP is released stimulating expression of GP2b3a
- TXA2 is released stimulating platelet aggregation
- GP2b3a receptors bind fibrinogen forming weak platelet plug that is then stabilized by coagulation cascade


Name the primary hemostasis disorders

- Immune thrombocytopenic purpura (ITP)
- Microangiopathic hemolytic anemias (thrombic thrombocytic purpura (TTP) and hemolytic uremic syndrome (HUS))
- Bernard-soulier and Glanzmann thrombasthenia (qualitative platelet disorders)


Who gets Immune thrombocytopenic purpura (ITP)?

- Most common cause of thrombocytopenia in children and adults
- Acute, normally self limiting following infection in children
- Chronic, appears in women of child bearing age (sometimes secondary to SLE), can be passed to fetus, temporary.


What are the lab findings in Immune thrombocytopenic purpura (ITP)?

- Decreased platelet count <50 k
- Normal PT/PTT
- Increased megakaryocytes on bone marrow biopsy


What is the treatment for Immune thrombocytopenic purpura (ITP)?

- Corticosteroids effective in children, adults normally relapse.
- IVIG for bleeding normally short lived.
- Spenectomy (refractory cases).


What causes thrombic thrombocytic purpura (TTP)?

- Decrease in ADAMTS13 (an enzyme that cleaves vWF multimers for eventual degradation) normally due to autoantibodies, commonly seen in women.
- vWF multimer leads to abnormal platelet aggregation and microthrombi formation--> Microangiopathic hemolytic anemia.


What is the cause of HUS?

- Caused by endothelial damage by drugs or infection (verotoxin)
- Commonly caused by E. Coli O157 H7 in children


What are the clinical findings of TTP and HUS?

- Microangiopathic hemolytic anemia
- Skin and mucosal bleeding and fever
- Renal insufficiency (HUS)
- CNS defects (TTP)


What are the laboratory findings for MHA?

- Thrombocytopenia with increased bleeding time
- Normal PT/PTT
- Anemia with schistocytes
- Increased megakaryocytes on bone marrow biopsy


What is the treatment for MHA?

- Plasmapheresis and corticosteroids particularly in TTP


What is the cause of Bernard-soulier and Glanzmann thrombasthenia?

- Bernard-soulier - Genetic GP1b deficiency
- Glanzmann thrombasthenia - Genetic GP2b3a deficiency


How does secondary hemostasis stabilize the weak platelet plug?

- Coagulation cascade generates thrombin
- Thrombin converts fibrinogen to fibrin
- Fibrin cross linking stabilizes the platelet thrombus


What activates secondary hemostasis? and which pathway is activated?

- Tissue factor (released by endothelial cells)--> factor 7 (extrinsic pathway, TP)
- Subendothelial collagen--> factor 12 (intrinsic pathway, TTP)
- Phospholipid suface of platelets and Ca


What causes hemophilia A?

- Factor 8 deficiency (X-linked recessive, and de novo mutation)


How does a patient with hemophilia A present and what are the laboratory findings?

- Deep tissue, joint and post surgical bleeding
- Increased PTT, normal PT
- Decreased factor 8
- Normal platelets and bleeding time


What is the treatment for hemophilia A?

- Recombinant factor 8


What is hemophilia B?

- Factor 9 deficiency
- Resembles hemophilia A


What is coagulation factor inhibitor? What is the most common factor? and How is it distinguished from hemophilia A?

- Developed autoantibody against coagulation factor.
- Most commonly factor 8
- PTT does not correct when mixed with normal plasma


What is Von Willebrand disease?

- Deficiency in vWF
- Most common inherited coagulation disorder
- Many variants, most common of which is autosomal dominant reduction in vWF


How does patient present with VWD?

- Mild mucosal and skin bleeding
- Deep tissue, joint and post surgical bleeding typically not seen


What are the lab findings for VWD?

- Increased bleeding time
- Increased PTT, normal PT (vWF stabilizes factor 8)
- Abnormal rictocetin test - Induces vWF GP1b binding and platelet aggregation


What is the treatment for VWD?

- Desmopressin (ADH analog) - increases vWF release for Weibel-palade bodies and alpha granules


How does vitamin K effect secondary hemostasis?

- Epoxide reductase released by the liver actives vitamin K--> vitamin K gamma
- Vitamin K gamma activates --> factors 2, 7, 9, 10, C, S


When does vitamin K deficiency occur?

- New borns - due to the absence of bacteria that produce vit K. Given vit K injection at birth to prevent hemorrhagic disease of the new born.
- Malabsorption, fat soluble vitamin
- Long-term antibiotic therapy, destruction of gut bacteria


What are other causes of secondary hemostasis and why do they occur?

- Liver disease - decreased production of coagulation factors and epoxide reductase (no activation of vitamin K)
- Large volume transfusions - dilution leads to relative deficiency


How does heparin induced thrombocytopenia occur?

- Heparin therapy induces platelet destruction causing the release of cytokines causing the activation of the remaining platelets--> thrombus


What are the causes of DIC?

- Obstetric complications --> Tissue thromboplastin from fetus into maternal blood--> coagulation
- Sepsis (E. Coli, N. menengitidis) - Endotoxin and cytokines (IL-1 and TNF) --> TF production
- Adenocarcinoma --> Mucin --> coagulation
- Acute promyelocytic leukemia --> Primary granules actives coagulation
- Rattlesnake bite --> venom activates coagulation


What are the laboratory findings for DIC?

- Decrease platelet count
- Increase PT/PTT
- Decrease fibrinogen
- Increase fibrin split products
- Microangiopathic hemolytic anemia


What is the treatment for DIC?

- Blood products and cryoprecipitate (contains coagulation factors)


What is the normal mechanism of fibrinolysis?

- Tissue plasminogen activator converts plasminogen to plasmin which cleaves fibrin and fribrinogen, destroys coagulation factors and blocks platelet aggregation
- Alpha-2 antiplasmin breaks down plasmin