Hematology - Bleeding Disorders Flashcards
List the differential for primary hemostatic disorders
- inability form platelet plug
Thrombocytopenia
- decreased production
- folate or B12 deficiency
- liver disease or alcohol
- bone marrow failure: aplastic anemia, chemotherapy, drug induced, myelodysplasia
- congenital: Alport, Fanconi
- infection: HIV, HCV, EBV, mumps
- sequestration from splenomegaly
- liver disease, malignancy, myelodysplasia
- Increased destruction
- immune: ITP, SLE, HIT
- non-immune: DIC, TTP, HUS, HELLP, pre-eclampsia
- Dilution
Platelet Dysfunction
- hereditary: GPIb or GPIIb/IIa deficiency
- acquired: aspirin, NSAID, alcohol, CKD
Von willebrane Disease
Vascular
- hereditary
- connective tissue disorder
- acquired
- henoch-schonlein purpura
- Cushing's syndromeList the differential for secondary hemostatic disorders
- inability to form fibrin clot Hereditary - Factor 8 deficiency: Hemophilia A, vWD - Factor 9 deficiency: Hemophilia B - Factor 11 deficiency Acquired - liver disease - DIC - vitamin K deficiency
Discuss the approach to bleeding disorders
Low Platelets on CBC
- consider thrombocytopenia causes
Normal PT/INR and aPTT with normal platelet count
- differential: platelet dysfunction, vWD, factor 13 deficiency, vascular integrity disorder
- platelet function analysis (PFA-100) and blood film to assess for platelet dysfunction
- factor 8 activity level, vWF antigen and ristocetin cofactor for vWD (all low)
Prolonged aPTT only
- hereditarory: Hemophilia A, Hemophilia B, vWD, factor 11 or 12 deficiency
- acquired: heparin, direct thrombin inhibitor (dabigatran)
- factor 8, 9, 11 assay
Prolonged PT/INR Only
- hereditary: factor 7 deficiency
- acquired: warfarin, vit K deficiency, liver disease
- factor 7 assay if does not improve with vit K
Prolonged PT/INR and Prolonged aPTT
- hereditary: prothrombin deficiency, fibrinogen deficiency
- acquired: severe liver disease, excessive anticoagulation with Warfarin or Heparin, direct Xa inhibitor (Apixaban, Rivaroxaban), DIC
- assess fibrinogen and D-Dimer for DIC (low fibrinogen and high D-Dimer suggest DIC)
Discuss the stages of hemostasis
Primary Hemostatis
- vessel injury results in collagen and subendothelial matrix exposure and release of vasoconstrictors
- blood flow is impeded and platelets come into contact with damaged blood vessel wal
- adhesion: platelets adhere to subendothelium via von Willebrand factor
- Activation: platelets are more activated resulting in change of shape and release of ADP and thromboxane A2
- aggregation: recruit and aggregrate more platelets forming platelet plug
Secondary Hemostasis
- Extrinsic (initiation): initiation of coagulation in vivo
- Intrinsic (amplification): amplification once coagulation has started via positive feedback
- both pathways converge on common pathway which results in thrombin formation and fibrin formation
Fibrin Stabilization
- conversion from soluble to insoluble and stable clot
Fibrinolysis
- clot dissolution via action of fibrinolytic system
Discuss the pathophysiology, presentation and management of immune thrombocytopenia
Pathophysiology
- primary: isolated platelet <100
- Secondary: due to another condition: HIV, HCV, SLE, CLL
- Drug-induced
- Have anti-platelet antibodies which bind to surface and lead to increased splenic clearance
Presentation
- minimal brusing
- mucocutaneous bleeding
Investigation
- thrombocytopenia
- increased number of megakarocytes on bone marrow aspirate
Management
- Emergency (bleed): steroids, antifibrinolytics (TXA), IVIg, platelet transfusion
Discuss the pathophysiology, presentation and management of heparin-induced thrombocytopenia
Pathophysiology - Immune mediated where antibody recognizes heparin and platelet factor 4 leading to platelet activation via Fc receptor and activation of coagulation system Presentation - 5-10d following heparin exposure - platelet count fall >50% - thrombosis Management - Stop heparin or LMWH - Initiate via non-heparin agent (fonduparinaux)
Discuss the pathophysiology, presentation and management of Thrombotic thrombocytopenic purpura
- adult Pathophysiology - deficiency in metalloproteinase that breaks down ultra-large vWF multimers: ADAMTS13 - congenital have absence of ADAMTS13 Presentation - thrombocytopenia - microcytic acquired hemolytic anemia - neurological symptoms Investigation - decreased platelets - Hemolysis: increased unconjugated bilirubin, increased LDH, decreased haptoglobin, negative Coombs Management - medical emergency - plasma exchance and steroids
Discuss the pathophysiology, presentation and management of hemolytic uremic syndrome
- children or elderly Pathophysiology - Shiga toxin from E coli Presentation - severe thrombocytopenia - AKI - Bloody diarrhea - GI prodrome - hemolytic anemia Investigation - Hemolysis: increased unconjugated bilirubin, increased LDH, decreased haptoglobin, negative Coombs MAnagement - supportive care with fluids
Discuss the pathophysiology, presentation and management of von Willibrand Disease
Pathophysiology - autosomal dominant - needed for platelet adhesion and chaperone for Factor VIII Presentation - bleeding history: mucocutaneous bleeding (easy bruising, epistacis, heavy menstrual bleeding, post-dental extraction) Management - Desmopressin - TXA
Discuss the pathophysiology, presentation and management of Hemophilia A
Pathophysiology - X-linked recessive Presentation - Prolonged bleeding - Hemarthrosis or deep muscle (hematoma) bleeding Management - desmopressin - Factor VIII concentrate - TXA
Discuss the pathophysiology, presentation and management of Hemophilia B
Pathophysiology - X-linked recessive Presentation - Prolonged bleeding - Hemarthrosis or deep muscle (hematoma) bleeding Management Management - Factor IX concentrate - TXA
Discuss the liver and Vitamin K dependent factors
Liver:
- all factors except for Factor VIII
- decreased fibrinogen
- Diminished anticoagulants and fibrinolysis
Vitamin K
- 1972 Canada vs Sovient
- Factor X, IX, VII, II and protein C and S
- Affected by Warfarin - vitamin K antagonist
- treatment with vitamin K 10mg IV or prothrombin complex concentrate
Discuss the pathophysiology, presentation and management of disseminated intravascular coagulation
- excessive, dysregulated release of plasmin and thronbin leading to intravascular coagulation and depletion of platelets, coagulation factors and fibrinogen Pathophysiology (OMITS) - Obstetric complication - Malignanc - Infection - Trauma - Shock Investigation - decreased platelets - prolonged INR, aPTT - decreased fibrinogen - increased D-dimer Management - Support - RBC tranfusion - Fresh frozen plasma if INR >1.5 or aPTT >38 - 10 units of cryoprecipitate if fibrinogen <1g/L
Discuss factor V leiden and protein C and S deficiency
Factor V Leiden
- activated protein C resistance
- results in resistance to activation of Factor Va
Protein C and S deficiency
- Factor C inactivates Factor Va and VIIIa using factor S as cofactor
Discuss massive transfusion protocol
- Occurs when patient has lost entire blood volume within 24hrs
- Require 4units pRBC for each volume blood lost
- Give 1 FFP for every 2u
- Require frequent monitoring of CBC, electrolytes (Ca included), INR and fibrinogen
