Bleeding disorders Flashcards
What are the bleeding disorders caused by vessel wall abnormalites? (6 total)
1) Infections (Meningococcemia)
2) Drug reactions
3) Scurvy and Ehlers-Danlos syndrome (defect in collagen)
4) Henoch-Schonlein purpura
5) Hereditary hemorrhagic telangiectasia (greatest risk for serious bleeding in GI)
6) Perivascular amyloidosis
What are the causes of thrombocytopenia?
1) Decreased production (aplastic anemia or leukemia)
2) Decreased survival rate (immunologic, DIC, microangiopathies, or mechanical injury)
3) Sequestration
4) Dilution
What disease is caused by IgG autoantibodies selective for platelet membrane glycoproteins IIb-IIIa or Ib-IX that results in thrombocytopenia?
Chronic Immune Throbocytopenic purpura (ITP)
What is the difference between chronic and acute immune thrombocytopneic purpura?
1) Acute- childhood disease, self-limited, follows viral illness
2) Chronic - common in women <40, relieved by splenectomy, diagnosis of exclusion
What drugs causes Drug induced thrombocytopneia and how do they induce this?
1) Quinine, Quinidine, and vancomycin
2) These drugs bind to platelet glycoprotiens and cause antigenic determinants that are recognized by antibodies
Why are megakaryocytes infected with HIV?
Megakaryocytes carry both CD4 and CXCR4; receptors for HIV
What are the differences between typical and atypical hemolytic uremic syndrome
1) Typical - due to infection of enterohemorrhagic E. coli
2) Atypical - due to a defect in Factor H, CD46, or Factor I (all prevent an excessive alternative complement pathway response)
What is the cause of thrombotic thrombocytopenic purpura?
1) Autoantibodies for ADAMTS13 (acquired)
2) Defect of ADAMTS13 (inherited)
What is the cause for hemolytic uremic syndrome?
1) Endothelial dysfunction that promotes platelet aggregation
What are the different specific defects of inherited defective platelet function?
1) Impaired adhesion (Bernard-soulier syndrome = defect in Gp1b)
2) Impaired aggregation (Glanzmann thrombasthemia = defective IIb-IIIa glycoprotien)
3) Impaired platelet secretion
What syndrome of platelet function impairment is associated impaired platelet adhesion?
Bernard-soulier syndrome- defect in Decreased Gp1b (platelet to vWF adhesion)
What syndrome of platelet function impairment is associated with impaired platelet aggregation?
Glanzmann thrombasthemia- defect in IIb-IIIa glycoprotein
Where is vWF produced? Where else is it found?
1) Endothelial cells and Kupffer cells
2) Alpha granules of platelets
What are the different types of Von Willebrand Factor Disease?
1) Type 1 - autosomal dominant; quantitative defect
2) Type 2 - qualitative defect (2A- autosomal dominant)
3) Type 3 - autosomal recessive; qualitative defect
What are the general features of vWF Disease?
1) Mild bleeding
2) Spontaneous bleeding from mucous membranes (epitaxis)
3) Normal platelet count
What are the general causes of bleeding disorders?
1) Vessel wall Abnormalities
2) Thrombocytopenia
3) Defective platelet function
4) Defective abnormalities in clotting factors
Why is there a prolonged PTT in vWF disease type 1 and 3?
1) Because vWF is closely associated with VIII by stabilizing it. If vWF is decreased or dysfunctional it causes a decrease in VIII (intrinsic coagulation factor)
What is the cause of Hemophilia A?
1) A X-linked recessive defect in coagulation factor VIII
2) Defect causes coagulation problem as well as inappropriate fibrinolysis due to decreased activation of thrombin activated fibrinolysis inhibitor (TAFI)
Clinical Features of Hemophilia A and B
1) Increased PTT
2) Severe bleeding with trauma
3) Spontaneous hemorrhaging of the joints
4) Petechiae are absent
5) Both are X linked recessive
What are the causes of DIC?
1) Release of tissue factor
( heat stroke, massive burns, massive trauma, obsteric complciations)
2) Wide spread injury to endothelial cells
(Sepsis, SLE, Neoplasms, hypoxia, and acidosis)
What cancers are most associated with DIC?
1) Acute promyleocytic leukemia and adenocarcinomas
What is the treatment for Hemophilia A and B?
1) A = recombinant VIII
2) B = recombinant IX
What is the treatment for DIC?
Treat the cause of DIC
What are the two results of DIC?
1) Wide spread thrombosis (commonly within the microvasculature)
2) Hemorrhagic diathesis
What does wide spread deposition of fibrin found in DIC result in?
1) Microangiopathic hemolytic anemia
What are the clinical features of Disseminated intravascular coagulation?
1) Schistocytes
2) Prolonged PT and PTT
3) Positive D dimer
4) Elevated fibrin degradation
X linked disease that causes immunodeficiency and thrombocytopenia with eczema
Wiskott-Aldrich Syndrome
What is the presentation of vWF disease?
1) Autosomal dominant or recessive (both sexes)
2) Petechiae
3) Prolonged PTT (due to vWF stabilizing VIII)
4) Abnormal platelet function
Pt presents with macrohemorrhage (hemarthroses, easy bruising, and increased PTT
Hemophilia A or B
Pt. presents with microhemorrhage (mucous membrane bleeding, epitaxis, petechia, purpura) increased bleeding time
Platelet disorder
Production of mutant factor V that is resistant to degradation b activated protein C
Factor V Leiden
Decreased ability to inactivate factors V and VIII
Protein C or S deficiency
