Hematology

• A patient with a platelet disorder will have what coagulation lab abnormality?
• Increased bleeding time (PT and PTT not reliably affected)
• What is the most common congenital bleeding disorder? And what are the different types
• Von Willebrand’s Disease
• Type I - Most common, reduced quantity of vWf, treat with desmopressin (for most patients) or cryoprecipitate
• Type II - Dysfunctional vWF , treat with desmopressin or cryoprecipitate
• Type III - Complete absence of vWF, desmopressin does not work, must use cryoprecipitate or Factor VIII replacement
• What bleeding disorders is cryoprecipitate helpful in?
• Von Willebrand’s, hypofibrinogenemia, hemophilia A
• What are the factors missing in Hemophilia A and Hemophilia B
• Hemophilia A = Factor VIII, prolongation of PTT
• Treat with factor VIII or cryo
• Hemophilia B = Factor IX, prolongation of PTT
• Treat with factor IX or FFP
• Coumadin = WEPT = Warfarin Extrinsic pathway PT
• PTT = intrinsic pathway
• A patient on coumadin undergoes surgery and following surgery platelets drop >50%, what tests to confirm the diagnosis? Treatment?
• Concern for Heparin Induced Thrombocytopenia
• Clinical suspicion with 4Ts score (thrombocytopenia, timing, thrombosis, and other possible causes)
• ELISA testing anti-platelet-factor-4 for initial screening

• Serotonin release assay for confirmation

• Stop heparin immediately with sufficient clinical suspicion
• Start safe anticoagulation (argatroban is classic; bivalirudin or fondaparinux also options)
• Patient presents with DVT and strong family history of DVT . What heritable blood clotting disorders would be on your differential?
• Factor V Leiden
• Prothrombin Gene Defect 20210
• Protein C and S Deficiency
• Antithrombin 3 Deficiency
• Hyperhomocystenemia
• A patient is started on Coumadin and develops skin necrosis, what is the name of this phenomena and what is its pathophysiology?
• Warfarin induced skin necrosis
• Seen in patients with protein C and S deficiency
• Short half-life of protein C and S (natural anticoagulants), leads to brief period of time where patient is hypercoagulable
• Important to bridge with Lovenox when starting coumadin
• Patients with hyperhomocysteinemia, how to treat this?
• Folic acid and B12
• How does antithrombin III deficiency present itself, and how do you treat it?
• They do not respond to heparin
• Treat with ATIII concentrate or FFP, prior to heparin admin
• Then start on long-term anticoagulant
• Mechanism of action of heparin? And how to reverse?
• Potentiates ATIII, makes it 1000x more potent
• Protamine to reverse

• Can cause hypotension and bradycardia

• What are characteristics of antiphospholipid syndrome, how do you diagnose and how do you treat it?
• History - symptoms of Lupus, prior DVTs, or recurrent pregnancy losses
• Will have prolonged PTT but are hypercoaguable
• Caused by antibodies to cardiolipin and lupus anticoagulant
• Treat with heparin bridge to coumadin
• What is mechanism of action of Warfarin?
• Inhibits VKORC (a protein that reduces Vitamin K to activate it)
• Inhibits creation of Factors X, IX, VII, II (1972) and protein and C and S
• Contraindicated in pregnant patients
• Warfarin reversal agents and their times to onset
• Administer Vit K (6 hours)
• FFP (<1 hour)
• Prothrombin Concentrate Complex (immediate)
• How do determine effectiveness of Lovenox
• Check factor Xa levels
• Unlike heparin, Lovenox is only weakly reversed by protamine
• Reversal agents for direct oral anticoagulants (DOACs)
• Dabigatran (Pradaxa)
• Can be reversed with dialysis
• And idarucizumab (Praxbind; monoclonal Ab that inactivates it)
• Apixaban (Eliquis) and rivaroxaban (Xarelto)

• Can be reversed with andexanet alfa (Andexxa; decoy- receptor for factor Xa inhibitor molecules)

• What is mechanism of action of tPA? How to reverse it?
• Activates plasminogen, breaks down fibrinogen
• Aminocaproic acid
• What are contraindications to using tPA?
• Absolute
• Active internal bleeding
• Recent CVA or neurosurgery
• Recent GI bleed, or intracranial pathology
• Relative contraindications
• Surgery past 10 days
• Recent organ biopsies, recent delivery
• Recent major trauma
• Uncontrolled hypertension
• Which coagulation factors are not synthesized in the liver?
• Factor VIII, and Desmopressin
• When to use FFP
• FFP has all coagulation factors

• Any coagulation disorder including Antithrombin III deficiency

• What factors are measured by PT/INR
• Measures external pathway - factors II, VII, IX, X (1972)
• Best test for liver synthetic function
• Goal INR of 2-3 generally in anticoagulated patients
• What factors are measured by PTT
• All except VII
• Goal of 60-90 in anticoagulated patients Quick Hits
• Thrombin (factor II) is key to coagulation
• Fibrinogen to fibrin
• Activates platelets
• Fibrin links platelets (GpIIb/IIIa molecules) to form a platelet plug
• Antithrombin III is key to anticoagulation
• Binds and inhibits thrombin
• Heparin activates AT-III
• What factors are made in liver?
• All except VIII and vWF
• Factor with the shortest half-life
• Factor VII
• What factors does warfarin block?
• Vit K dependent factors: II, VII, IX, X, protein C and S
• What does cryo contain?
• High concentrations of vWF, VIII, and fibrinogen
• What is in FFP
• All clotting factors, some fibrinogen

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