Hemostasis and Related Disorders Flashcards
Primary Hemostatis Steps
- Transient vasoconstriction of damaged vessel (endothelin release)
- Platelet adhesion to surface of disrupted vessel
- vWF (from Weibel Palade bodies of endothelial cells and alpha granules of platelets) binds exposed subendothelial collagen
- platelets bind vWF using GPIb receptor - Platelet degranulation
- ADP released from platelet dense grandules - promotes exposure of GPIIb/IIIa receptor on platelets (aggregation)
- TXA2 is synthesized by platelet COX and released –> promotes platelet aggregation - Platelet aggregation
- aggregate at site of injury using GPIIb/IIIa fibrinogen as a linking molecule
- secondary hemostasis stabilizes platelet plug
Weibel-Palade Bodies
Of endothelial cells
Contain P-selectin and vWF
Immune Thrombocytopenic Purpura
Autoimmune production of IgG against platelet antigens (eg. GPIIb/IIIa) - produced by plasma cells in spleen
Antibody-bound platelets are consumed by splenic macrophages –> thrombocytopenia
Acute Form: arises in children after viral infection or immunization; self limited
Chronic Form: arises in adults usu women; may be primary or secondary SLE
Lab findings:
- decreased platelet count (<50K/microL)
- normal PT/PTT
- increased megakaryocytes on bone marrow
Tx. Corticosteroids, IVIG, splenectomy
Microangiopathic Hemolytic Anemia
Pathologic formation of platelet microthrombi in small vessels
Platelets are consumed in formation of thrombi
RBCs are sheared as they cross microthrombi –> hemolytic anemia with schistocytes
Seen in TTP and HUS
Clinical Findings:
- skin and mucosal bleeding
- microangiopathic hemolytic anemia w/in vessels
- fever
Lab Findings:
- thrombocytopenia with increased BT
- normal PT/PTT
- anemia with schistocytes
- increased megakaryocytes on bone marrow biopsy
Thrombotic Thrombocytopenic Purpura
Microangiopathic hemolytic anemia
Due to decreased ADAMTS13, an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation
Large multimers lead to abnormal platelet adhesion –> microthrombi
CNS abnormalities more common than in HUS
Hemolytic Uremic Syndrome
Microangiopathic hemolytic anemia due to endothelial damage by drugs or infection
Classically seen in children with E. Coli O157:H7 dysentery (due to undercooked beef) - E. coli verotoxin damates endothelial cells resulting in platelet microthrombi
Renal insufficiency is more common than in TTP
Bernard Soulier Syndrome
Due to genetic GPIb deficiency;
Impaired platelet adhesion because cannot bind vWF
Blood smear shows mild thrombocytopenia with enlarged platelets “Big Suckers”
Glanzmann Thrombasthenia
Due to genetic GPIIb/IIa deficiency; platelet aggregation is impaired
PT
Measures extrinsic pathway
Factor VII
PTT
Measures intrinsic pathway
XII, XI, IX, VIII
Hemophilia A
Genetic VIII deficiency; X linked recessive
Presents with deep tissue, joint and post-surgical bleeding
Increased PTT, normal PT
Decreased factor 8
Normal platelet count and BT
Hemophilia B
Genetic factor IX deficiency
Resembles Hemophilia A except with low levels or factor 9
von Wildebrand Disease
Most common inherited coagulation disorder
Quantitative and qualitative subtypes exist, but most common is decreased vWF levels
Presents with mild mucosal and skin bleeding due to impaired platelet adhesion
Lab findings:
- increased bleeding time
- increased PTT, but normal PT
- abnormal ristocetin test
Tx. is desmopressin (ADH analog) that increases vWF release from Weibel Palade bodies of endothelial cells
Risocetin Test
Ristocetin induces platelet agglutination by causing vWF to bind platelet GPIb
Lack of vWF –> impaired agglutination –> abnormal test
Vitamin K Deficiency
Vit K is activated by epoxide reductase in the liver; activated vit K carboxylates factors II, VII, IX, X and proteins C and S; gamma carboxylation is necessary for factor function
Deficiency occurs in:
- newborns due to lack of GI colonic bacteria that normally synthesize
- long term antibiotic therapy
- malabsorption
