What is the most common cause of primary polycythemia?
The primary pathway for the initiation of coagulation is what?
Tissue factor (extrinsic) pathway
Which test assesses the intrinsic and common clotting pathways; also monitors the treatment effect of Heparin?
Which test is used to monitor treatment effect of coumadin as well as the extrinsic and common coagulation pathways?
What are the platelet counts and tests of coagulation (PT, PTT) like in bleeding disorders caused by vessel wall abnormalities?
Which infections are associated with vessel wall abnormalities that can cause bleeding?
- Meningococcemia --> can be catastrophic if not recognized clinically
- Septicemia + infective endocarditis
Henoch-Schonlein purpura is a cause of bleeding due to vessel wall abnormalities and is characterized by what signs/sx's?
- Purpuric rash
- Colicky abdominal pain
- Acute glomerulonephritis
Serious bleeding is most often associated with what inherited disorder causing vessel wall abnormalities?
Hereditary hemorrhagic telangiectasia (Weber-Osler-Rendu syndrome)
What is the most frequent symptom/presentation of hereditary hemorrhagic telangiectasia?
Which infectious agents can infect megakaryocytes leading to decreased platelet production (thrombocytopenia)?
HIV; one of the most common hematologic manifestations of HIV
How may alloantibodies against platelets be generated?
When platelets are transfused or cross placenta from fetus ---> mother
What are the 2 most important non-immunologic causes of decreased platelet survival leading to thrombocytopenia?
- Thrombotic microangiopathies (TTP and HUS)
Chronic immune thrombocytopenic purpura (ITP) is most commonly seen in whom?
Young women <40 y/o and is 3x more likely in females than males
What is the pathogenesis of chronic immune thrombocytopenic purpura (ITP); which antibody is most often seen?
- Due to autoantibodies (IgG) against platelets
- Anti-platelet Abs are recognized by IgG Fc receptors expressed on phagocytes ---> ↑ platelet destruction
What is seen in the bone marrow and peripheral blood with chronic immune thrombocytopenic purpura (ITP)?
- Marrow reveals moderately ↑ number of megakaryocytes
- Peripheral blood reveals abnormally large platelets (megathrombocytes)
What are the clinical signs/sx's of chronic immune thrombocytopenic purpura (ITP); often there is a history of what?
- Insidious onset characterized by bleeding into the skin and mucosal surfaces
- Cutaneous bleeding in the form of petechiae and ecchymoses
- Often there is hx of epistaxis, easy bruising, gum bleding and hemorrhages into soft tissues w/ minor trauma
The thrombocytopenia of chronic immune thrombocytopenic purpura (ITP) is markedly improved following what?
How is the diagnosis of chronic immune thrombocytopenic purpura (ITP) made?
Diagnosis of exclusion after all other causes of thrombocytopenia ruled out
How does acute ITP differ from chronic ITP in terms of population affected and pathogenesis?
- Mainly affects children, occurring equally in males and females
- Sx's appear abruptly, 1-2 weeks after self-limited viral infection
- Acute ITP, unlike chronic, is self-limited and usually spontaneously resolves within 6 months
Chronic ITP may sometimes first manifest with what signs/sx's?
Melana, hematuria, or excessive menstrual flow
What are 2 serious and sometimes fatal complications of chronic ITP?
Subarachnoid hemorrhage and intracerebral hemorrhage
Which 3 drugs are most commonly indicated in causing drug-induced thrombocytopenia?
Which type of heparin-induced thrombocytopenia is most clinically significant and explain what occurs?
- Type II, begins 5-14 days after initiation of therapy
- Antibodies recognize complexes of heparin and platelet factor 4
- Leads to activation of platelets and promotes thrombosis EVEN in the setting of thrombocytopenia
What are the complications which may arise with heparin-induced thrombocytopenia, type II?
- Clots within large arteries may lead to vascular insufficiency and limb loss
- Emboli from DVT's can cause fatal pulmonary thromboembolism
*This is thrombosis occurring in the setting of thrombocytopenia, which is paradoxical to what should be happening.
Explain how HIV can cause both decreased production and survival of platelets?
- HIV binds CD4 and CXCR4 on megakarytocytes; causing these cells to become prone to apoptosis and ↓ platelet production
- HIV causes B-cell hyperplasia, predisposing to the development of autoantibodies, which may opsonize platelets, promoting their destruction
Which feature of TTP and HUS is not of primary importance like it is in DIC?
Activation of the coagulation cascade is NOT of primary importance; so the PT and PTT = normal
Thrombotic thrombocytopenic purpura (TTP) is due to a deficiency in what?
ADAMTS13 (aka "vWF metalloprotease)
What is the classic pentad of findings associated with TTP?
- Microangiopathic hemolytic anemia
- Transient neuro deficits
- Renal failure
How do typical vs. atypical HUS differ from eachother?
- Typical is highly assoc. w/ E. coli O157:H7 infection (shiga-like toxin) most commonly affecting children/older adults
- Atypical is assoc. w/ defects in complement factor H, membrane cofactor protein (CD46) or factor I ---> which normally prevent activation of alternative complement pathway
Bernard-Soulier Syndrome illustrates the consequences of which type of platelet dysfunction; caused by what?
- Defective adhesion of platelets to subendothelial matrix
- AR inherited deficiency of platelet membrane glycoprotein complex Ib-IX; which is a receptor for vWF