Hemostasis Disorders Flashcards
Which factors are tested for in the prothrombin time? What about for the partial thromboplastin time?
- prothrombin time (PT): extrinsic and common pathways; factors VII, X, V, II, and I
- partial thromboplastin time (PTT): intrinsic and common pathways; all factors except factors VII and XIII
What are the two main coagulation disorders? Will PT and/or PTT be increased in each? What general symptoms do disorders of coagulation lead to?
- hemophilia (A or B): A is a deficiency in factor VIII, B in factor IX; both result in a defective intrinsic response, and will increase PTT; both are X-linked recessive
- vitamin K deficiency: deficiency in factors II, VII, IX, X, C, and S; results in a defective extrinsic and intrinsic response, and will increase both PT and PTT
- coagulation disorders result in deep bleeding and delayed/prolonged post-surgical bleeding, hemarthroses; additionally, large bruising (usually no petechiae)
What are the four main platelet disorders? How are platelet count and bleeding time affected by each? What general symptoms do disorders of platelets lead to?
- Bernard-Soulier syndrome: mildly lowered PC, raised BT
- Glanzmann thrombasthenia: normal PC, raised BT
- immune thrombocytopenia/immune thrombocytopenic purpura (ITP): MC platelet disorder; lowered PC, raised BT
- thrombotic thrombocytopenia purpura (TTP): lowered PC, raised BT
- platelet disorders result in superficial bleeding (epistaxis and gum bleeding) and immediate mild post-surgical bleeding; additionally, petechiae and small bruising
What are the two main mixed platelet and coagulation disorders? How are platelet count, bleeding time, prothrombin time, and partial thromboplastin time affected by each?
- von Willebrand disease: MC inherited coagulation disorder; normal PC, increased BT, normal PT/extrinsic, increased PTT/intrinsic
- disseminated intravascular coagulation (DIC): lowered PC, increased BT, increased PT, increased PTT
What is Bernard-Soulier syndrome? What do we see on a blood smear in this disorder?
- (a qualitative platelet disorder; results in mildly lowered PC, elevated BT)
- Bernard-Soulier syndrome is an AR genetic defect in platelet’s glycoprotein GpIb, resulting in defective platelet adhesion to vWF
- blood smear: platelets tend to be slightly larger than normal (a macrothrombocytopenia) and also have a decreased life span
What is Glanzmann thrombasthenia? What do we see on a blood smear in this disorder?
- (a qualitative platelet disorder; results in normal PC, elevated BT)
- Glanzmann thrombasthenia is a genetic defect in platelet’s glycoprotein GpIIb/IIIa, resulting in defective platelet aggregation (platelet-to-platelet binding)
- blood smear: normal platelets, but no platelet clumping
What is immune thrombocytopenia? What is it also known as? What do we see on bone marrow biopsy in this disorder?
- (a platelet disorder; results in lowered PC, elevated BT)
- immune thrombocytopenia is AKA immune thrombocytopenic purpura (ITP); it is the MC platelet disorder in kids (usually acute and self-limiting) and adults (usually chronic)
- caused by anti-GpIIb/IIIa antibodies; antibody bound platelets get consumed by splenic macrophages
- may be triggered by a viral illness
- bone marrow biopsy: increased megakaryoctes
What is thrombotic thrombocytopenic purpura? What do we see in the lab and on bone marrow biopsy in this disorder? What is the classic pentad of resulting symptoms?
- (a platelet disorder; results in lowered PC, elevated BT)
- thrombotic thrombocytopenic purpura (TTP) is a deficiency of ADAMTS13 (a vWF metalloprotease) via auto-antibodies or mutation, leading to defective degradation of large vWF multimers
- the increase in vWF multimers consumes platelets, so aggregation and thrombosis increase here, but in the wrong spots; platelet survival is decreased
- lab: schistocytes, increased LDH, increased megakaryocytes on bone marrow biopsy
- pentad: neurologic symptoms, renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia
What is microangiopathic hemolytic anemia? What three conditions is it associated with?
- this is a condition resulting from the formation of intravascular micothrombi, partially occluding vessels, and causing the shearing of RBCs as they pass through
- results in schistocytes and lowered free floating PC
- seen in thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (via E. coli O157:H7), and DIC
What is von Willebrand disease? Why does it affect both primary and secondary hemostasis? How is it diagnosed? How is it treated?
- (mixed disorder resulting in normal PC, increased BT, normal PT, increased PTT if severe); MC inherited coagulation defect
- von Willebrand disease is an autosomal DOMINANT inherited defect in vWF
- vWF is an important carrier/protecting factor for factor VIII (without vWF, free-floating VIII degrades very quickly), which is why severe cases also show an increase in PTT/intrinsic
- diagnose with decreased agglutination seen in a ristocetin test (ristocetin activates vWF to bind to GpIb)
- treat with DDAVP (desmopressin!), which actually increases the release of vWF from the endothelial Weibel-Palade bodies (works for type I disease, which is a partial quantity defect)
What is DIC? What can cause it? What is the best screening test for this disorder?
- (mixed disorder resulting in lowered PC, increased BT, increased PT, increased PTT)
- disseminated intravascular coagulation is the pathologic activation of clotting/thrombus formation, consuming these proteins in the process
- the resulting microvascular thrombi leads to ischemia, infarction, and microangiopathic hemolytic anemia
- causes: STOP Making New Thrombi: Sepsis, Trauma, Obstetric complications (such as HELLP and amniotic fluid embolism), acute Pancreatitis, MAlignancy, NEphrotic syndrome, Transfusion, rattle-snake bite
- best screening test is D-dimer
What is heparin induced thrombocytopenia? How soon after starting therapy does it arise?
- HIT is a complication of heparin anticoagulation therapy
- it is a consumptive coagulopathy (similar to TTP, HUS, HELLP, DIC) resulting from the formation of a heparin-PF4 complex on platelets, which get destroyed by IgG antibodies
- consumptive coagulopathies cause thrombosis and bleeding/thrombocytopenia
- arises 5-10 days after heparin therapy is initiated
