Hemolytic Disorders Flashcards
Useful Laboratory Studies in Primary Disorders
Platelet count: normal is 150-400 (
Immune Thrombocytopenic Purpura (ITP)
Primary Hemostasis Disorder
Autoimmune production (from spleen) of IgG against platelet antigens (GPIIb/IIIa)
Antibody-bound platelets are consumed by splenic macrophages
Thrombocytopenia
Acute (viral infections in children) and chronic forms (adults, usually women)
Decreased platelet count, normal PT/PTT (coagulation not affected), increased megakaryocytes on bone marrow biopsy
Treat with corticosteroids or temporarily with IVIG. Last resort: splenectomy
Microangiopathic Hemolytic Anemia
Primary Hemostasis Disorder
Platelet microthrombi in small vessels (platels are consumed)
RBCs are sheared as they cross (schistocytes)
Seen in TTP and HUS (e.coli toxin damages endothelial cells and causes the microthrombi)
Skin/mucosal bleeding, anemia (namesake), fever, renal insufficiency, CNS abnormalities
Thrombocytopenia with increased bleeding time, NORMAL PT/PTT (coagulation cascade not affected), anemia with schistocytes, increase in megakaryocytes on bone marrow biopsy
Treat with plasmapheresis and corticosteroids
Thrombocytopenic purpura (TTP)
Primary Hemostasis Disorder
Decreased ADAMTS13 (enzyme that cleaves vWF multimers)
Large, uncleaved vWF multimers lead to abnormal platelet adhesion
Results in microthrombi
Decreased ADAMTS13 is due to acquired antibody, commonly seen in adult females (classic patient)
Bernard-Soulier syndrom
Primary Hemostasis Disorder
Genetic GPIb deficiency
Platelet adhesion impaired
Blood smear shows mild thrombocytopenia with enlarged platelets (immature platelets), “Big-Suckers”
Glanzmann thrombasthenia
Primary Hemostasis Disorder
Genetic GPIIb/IIIa deficiency
Platelet aggregation is impaired
ASA’s effect on platelets
Primary Hemostasis Disorder
Qualititative
ASA irreversibly inactivates COX
Lack of TXA2 impairs aggregation
Useful Laboratory Studies in Secondary Disorders
Prothrombin time (PT): measures extrinsic (factor VII) and common (factors II, V, X, and fibrinogen) pathways of coagulation cascade Partial prothrombin time (PTT): measures intrinsic (factors XII, XI, IX, VIII) and common (factors II, V, X, and fibrinogen) pathways of coagulation cascade
Hemophilia A
Secondary Hemostasis Disorder
Genetic factor VIII deficinecy
X-linked recessive (predominantly in males), or de novo mutation
Present with deep tissue, joint, and post-surgical bleeding
Increased PTT, normal PT, decreased FVIII levels, normal platelet count and bleeding time
Treat with recombinant FVIII
Hemophilia B
Secondary Hemostasis Disorder
Genetic factor IX deficiency
Christmas Disease
Resembles hemophilia A, except with factor IX levels
Coagulation Factor Inhibitor
Secondary Hemostasis Disorder
Acquired antibody against a coagulation factor, resulting in impaired factor function.
Anti FVIII is most common
Clinical and lab findings are similar to hemophilia A
PTT does not correct upon mixing normal plasma with patient’s plasma due to inhibitor (there is just too much antibody) whereas PTT does correct in hemophilia A
VonWillebrand Disease
Secondary Hemostasis Disorder
Genetic vWF deficiency
Most common inherited disorder
Multiple subtypes (quantitative and qualitative defects)
Mild mucosal and skin bleeding (low vWF impairs platelet adhesion)
Increased bleeding time (poor platelet adhesion), increased PTT, normal PT, decreased FVIII half-life (vWF stabilized FVIII)
However, deep tissue, joint, and postsurgical bleeding are usually not seen (unusual)
Abnormal ristocetin test: ristocetin induces platelet agglutination by causing vWF to bind platelet GPIb
Lack of vWF -> impaired agglutination -> abnormal test
Treat with desmopressin (ADH analog) which increases vWF release from WP bodies in endothelial cells
Vitamin K deficiency
Secondary Hemostasis Disorder
Disrupts multiple coagulation factors
Activated vitamin K gamma-carboxylates 2, 7, 9, 10, and protein C & S
Deficiency in newborns (don’t have GI bacteria), long-term antibiotics, and malabsorption
Other Causes of Abnormal Secondary Hemostasis
Liver failure: decreased production of coagulation factors, and decreased activation of vitamin K. Followed via PT test
Large volume transfusion: dilutes coagulation factors, relative deficiency
Heparin-Induced Thrombocytopenia (HIT)
Heparin forms complex with PF4 on platelet surface
Body makes antibodies to this complex, platelets are consumed in the spleen
Platelet destruction is secondary to heparin therapy
Fragments of destroyed platelets may activate remaining platelets leading to thrombosis
Disseminated Intravascular Coagulation (DIC)
Pathologic activation of coagulation cascade
Widespread microthrombi leading to ischemia and infarction
Consumption of platelets and factors results in bleeding (IV sites and mucosal surface)
SECONDARY TO ANOTHER DISEASE PROCESS (pregnancy, sepsis via E.coli or N.meningitidis), adenocarcinoma, leukemia, rattlesnake bite
Decreased platelet count, increased PT/PTT, fibrinogen, microaniopathic hemolytic anemia, elevated fibrin split products
*Elevated D-dimer is best screening test for DIC
Treat the underlying cause and transfusing blood products
Disorders of Fibrinolysis
Plasmin overactivity resulting in excessive cleavage of serum fibrinogen
Radical prostatectomy: release of urokinase activates plasmin
Cirrhosis of liver: reduced production of a2-antiplasmin
Present with increased bleeding (RESEMBLES DIC)
Increased PT/PTT (plasmin destroys coagulation factors)
Increased bleeding time with NORMAL platelet count
Increased fibrinogen split products WITHOUT D-dimers (fibrinogen, not fibrin, is being split)
Protein C or S deficiency
Hypercoagulable State
Autosomal dominant
Decreases negative feedback on the coagulation cascade
Proteins C and S normally inactivate factors V and VIII
Increased risk for warfarin skin necrosis (initial warfarin therapy results in temp deficit of protein C and S relative to factors II, VII, IX, and X). If there is a preexisting protein C or S deficiency, severe deficiency results with inital warfarin and there is a greater risk of thrombosis particularly in the skin
Factor V Leiden
Hypercoagulable State
Mutated form of factor V that lacks the cleavage site for deactivation by proteins C and S
Most common inherited cause of hypercoagulable state
Prothrombin 20210A
Hypercoagulable State
Inherited point mutation in prothrombin
Results in increased gene expression of prothrombin and excessive production
Increased prothrombin results in increased thrombin
Promotes thrombus formation
ATIII deficiency
Hypercoagulable State
Decreases the protective effect of heparin-like molecules produced by the endothelium, increasing risk of thrombus
Heparin-like molecule normally activate ATIII, which inactivates thrombin and coagulation factors
In deficiency, PTT DOES NOT RISE with standard heparin dosing (because hep acts via ATIII)
Oral Contraceptives
Hypercoagulable State
Estrogen induces increased production of coagulation factors
Increases risk of thrombosis
