Bleeding Disorders Flashcards
What are the phases of homeostasis in clot formation?
(1) vasocontriction - endothelin release at the site of injury causes reflex vasoconstriction; (2) platelet adhesion - von Willebrant Factor (protein layer that acts like glue when endothelium is breeched) causes platelets to adhere and release cytokines; (3) platelet aggregation - activation of cytokines (ADP and TXA2) cause platelets to aggregate and form a platelet plug at the site of injury; (4) release of t-PA (fibrinolysis) and thrombomodulin (blocks coagulation cascade) prevent the clot from growing too large
What is the intrinsic pathway in the coagulation cascade?
includes Factors XII, XI, IX, and VIII to Factor X (more stable because it produces more fibrin) => affects the Partial Thromboplastin Time (PTT)
What is the extrinsic pathway in the coagulation cascade?
includes tissue factor and Factor VII (unstable because tissue factor is short-lived) => affects Prothrombin Time (PT)
What is the role of clotting factors in clot formation?
stabilize the platelet plug
What are clotting factors?
proteins produced in the liver with the help of Vitamin K
What is fibrin?
insoluble fibers that help to reinforce the platelet plug
Which therapies that reduce clot formation act on platelets?
aspirin and clopidogrel (Plavix)
How does aspirin prevent clot formation?
blocks TXA2 - prevents platelets from aggregating => platelet plug cannot form
How does clopidogrel (Plavix) prevent clot formation?
blocks ADP - prevents platelets from aggregating => platelet plug cannot form
How does Vitamin K deficiency contribute to bleeding?
Vitamin K deficiency causes a decrease in Factor VIII which, in turn, stops the intrinsic clotting cascade (liver will not produce clotting factors without Vitamin K)
How does coumadin (Warfarin) prevent clotting?
acts as an indirect anticoagulant => reduces Vitamin K
How do rivaroxaban (Xarelto) and apixaban (Eliquis) prevent clotting?
act as direct anticoagulant => directly inhibit Factor X (think rivaroXaban and apiXaban = X for Factor X)
How does dabigatran (Pradaxa) prevent clotting?
directly inhibits thrombin production
What is the mechanism of tissue plasminogen factor (t-PA) in preventing clots?
breaks up only fresh clots (acts only on newly released fibrin) - has to be given within 3.5 hours of a thrombotic stroke
What does the presence of D-Dimer indicate?
recency of a clot - reflects active/fresh coagulation
What is the International Normalized Ratio (INR)?
a standardized tissue factor that is added to a test tube of blood to test time to formation of fibrin clot
How is prothrombin time (PT) used in Warfarin management?
Warfarin has strongest effects on Factor VII (has the shortest half-life of all Factors) - affects the extrinsic pathway of the clotting cascade
What is the best indicator of Warfarin level?
prothrombin time (PT)
What is the best indicator of Heparin level?
partial thromboplastin time (PTT)
How is partial thromboplastin time (PTT) used in Heparin management?
Heparin has strongest effects on Factors IX and XI - affects the intrinsic pathway of the clotting cascade
What is the role of Xarelto/Eliquis in management of clotting disorders?
used for non-valvular A-fib, DVTs and PE - affect both PT and PTT, but extent of effect is unreliable => no good correlation between drug level and anticoagulant effect - give standard doses and hope for no negative effects
What is the Rule of 10 for remembering coagulation tests?
drug name and lab acronym add up to 10 letters:
(1) Heparin + PTT = 10 letters
(2) Coumadin + PT = 10 letters
What are the tests for tracking primary hemostasis (disorders involving platelets)?
(1) CBC (platelets) - normal = 150,000 to 450,000 (# of platelets can be normal but platelet function can be abnormal)
(2) bleeding time (controlled, superficial cut) - normal = < 10 minutes (provides indication of platelet function but not used in practice)
What are the tests for tracking secondary hemostasis (disorders involving clotting factors)?
measure the time it takes for fibrin clot to form
(1) PT/INR - extrinsic pathway - normal = 11-14 seconds (dependent on tissue factor’s effect on Factor VII - tissue factor is extrinsic/does not exist in the blood and has to be added to the test tube)
(2) PTT - intrinsic pathway - normal = 25-35 seconds (depends on Factors XII, XI, IX, and VII - intrinsic/already exist in the blood)
What are the characteristics of bleeding due to primary hemostasis disorders (i.e., disorders of platelets)?
superficial (mucosal) bleeding (epistaxis, gingival, vaginal); skin bleeding - petechia (< 0.5 cm, purpura 0.5-1. cm) => non-blanchable (out of the blood vessels)
What are the causes of bleeding due to primary hemostasis disorders (i.e., disorders of platelets)?
Inherited: von Willebrant Disease
Acquired: idiopathic thrombocytopenic purpura (ITP - autoimmune disorder against platelets), drug-induced (aspirin, NSAIDs, clopidogrel), splenomegaly, viral infections (HIV, HCV), uremia
What are the characteristics of bleeding due to secondary hemostasis disorders (i.e., disorders of clotting factors)?
deep bleeding in joints (hemarthrosis), bleeding/bruises in muscles and retroperitoneal cavity
What are the causes of bleeding due to secondary hemostasis disorders (i.e., disorders of clotting factors)?
hemophilia, Vitamin K deficiency (malnutrition), drug-induced (Warfarin/Heparin), cirrhosis (dysfunctional liver cannot produce enough clotting factors)
What is idiopathic thrombocytopenic purpura (ITP)?
an autoimmune disease, sometimes preceded by a viral illness - body develops antibodies to one’s own platelets (antibodies cover platelets, macrophages then carry platelets to spleen for destruction) => dysfunction in the number of platelets, but platelet function is normal (normal RBCs, WBCs, and clotting factors)
What are the signs and symptoms of ITP?
mostly asymptomatic or platelet-type/superficial bleeding
What is the treatment for ITP?
severe thrombocytopenia (< 50,000) => prednisone (prevents macrophages from grabbing antibodies on platelets)
repeated episodes => splenectomy (prevents destruction of platelets)
What is von Willebrant Disease (VWD)?
most common inherited bleeding disorder (autosomal dominant inheritance - not on sex chromosome, only need 1 defective gene to cause disease - 50% likelihood with each pregnancy/male or female) - deficiency in von Willebrant factor => abnormality in platelet function, but platelet number is normal - leads to prolonged PTT
How is VWD diagnosed?
normal platelet number, prolonged bleeding time (> 10 minutes), PTT may be prolonged, PT normal, VWF level is decreased
What is the treatment for VWD?
desmopressin (deamino-d-arginine vasopressin - DDAVP) - a synthetic ADH (given IV or intra-nasally) => induces endothelial cells to release VWF from stores (those affected by VWD do not completely lack VWF, it is just not released)
What is hemophilia?
x-linked recessive disorder (carried on sex chromosome - need 2 defective genes to cause disease and only 1 to be carrier) - 2 types:
(1) A - deficiency of Factor VIII
(2) B - deficiency of Factor IX - less common
What are the signs and symptoms of hemophilia?
only affects males, hemarthrosis (most commonly the knee), progressive joint destruction, retroperitoneal bleed, intracranial bleed => bleeding time is normal (affects Factors, not platelets)
How is hemophilia diagnosed?
platelet count is normal, bleeding time is normal, PTT increased (prolonged), PT is normal, Factor VIII or IX is decreased
What is the treatment for hemophilia?
clotting factor replacement (recombinant FVIII or FIX):
- given 3X per week (for life) - prophylactically
- give additional Factors when injury occurs
- heavy bleeding - need to give plasma
- acute hemarthrosis - analgesia and immobilization
What distinguishes the clinical presentation of VWD and hemophilia?
VWD - both male and female patients, bleeding is superficial
hemophilia - affects only male patients, bleeding is deep
