Hematology Flashcards
Virchows Triad
Virchow’s triad
Vessel injury
Stasis (worse with hypovolemia)
Abnormal coagulation
- Congenital- anti-thrombin-3-deficiency, protein C/S deficiency, dysfibrinogenemia, plasminogen diseases
- Acquired- lupus anticoagulant, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria, BCP/estrogen use, polycythemia vera, sepsis
Steps of primary hemostasis
Formation of platelet plug: 1. Adhesion of platelets to damaged vascular wall (requires VIII:vWF) 2. Activation of platelets (requires thrombin (IIa) 3. Aggregation of platelets (requires ADP/TXA2) 4. Production of fibrin (requires extrinsic, intrinsic and final common pathway factors)
Steps of secondary hemostasis
Production of fibrin, coagulation 1. Initiation of thrombin generation (though TF on fibroblasts-extrinsic) 2. Amplification of thrombin generation 3. Propagation of thrombin generation 4. Fibrin formation
Extrinsic pathway
37 cents–Damage outside the vessel triggers release of thromboplastin (III), the primary initiator of coagulation. TP activates VII. VII+Ca(IV) on surface of platelet—X is activated.
Vit K dependent
Intrinsic Pathway
Intrinsic path: $12—$11.98—Trauma to the blood itself or exposure of the blood to collagen activates IX. IX/VIII:C/Ca++ on platelet surface activates X.
Final common pathway of coagulation cascade
Final Common Path: 5(V) & dime(X) for 1 or 2 dollars on the 13th of the month. X, V, & Ca on platelet surface convert prothrombin (II) to thrombin (IIa). IIa converts fibrinogen (I) to fibrin(Ia)—Ia + XIII, fibrin cross-linking occurs.
Coagulation Cascade
Extrinsic path: 37 cents–Damage outside the vessel triggers release of thromboplastin (III), the primary initiator of coagulation. TP activates VII. VII+Ca(IV) on surface of platelet—X is activated.
Intrinsic path: $12—$11.98—Trauma to the blood itself or exposure of the blood to collagen activates IX. IX/VIII:C/Ca++ on platelet surface activates X.
Final Common Path: 5(V) & dime(X) for 1 or 2 dollars on the 13th of the month. X, V, & Ca on platelet surface convert prothrombin (II) to thrombin (IIa). IIa converts fibrinogen (I) to fibrin(Ia)—Ia + XIII, fibrin cross-linking occurs.
What are DOACs?
Direct-acting oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban are not required to have monitoring but are sensitive to changes in renal function and are associated with poorer adherence.
Coagulation half lives and initiation of Warfarin therapy, which factor is reduced first?
Early reduction VII 🡪 X 🡪 IX 🡪 II
Anticoagulant effects occur in ~2 days vs a minimum of 4-6 days for an initial antithrombotic effect (peak @5-7days)
Protein C
Protein C: autoprothrombin IIA and blood coagulation factor XIV, is a zymogen
Protein C has shortest half life of vit K dependent depend proteins
When on Warfarin- pt loses protein C much more quickly than the procoagulation effects of VII, II, IX, and X🡪 Warfarin necrosis
Prevented by bridging with Heparin
Protein C and S
Endothelial cell protein C receptor bind complex🡪Thrombin-Thrombomodulin complex activates Protein C🡪C+S (free protein S on endothelial or platelet phospholipids surfaces) degrade factors Va and VIIIa 🡪prev conversion of fibrinogen to fibrin
When Thrombin bound to TM, it loses its procoag fxn
4 classes of anticoagulants
- Vitamin K antagonists (coumarin anticoagulants)
- Warfarin
- Low molecular weight heparins (LMWH)-
- enoxaparin (Lovenox)
- dalteparin (Fragmin)
- heparin
- Direct thrombin inhibitors
- bivalirudin (Angiomax) – powder for injection
- argatroban (Acova) - injectio
- dabigatran (Pradaxa) – oral capsule
- antithrombin III (Thrombate III) – powder for injection
- Factor Xa Inhibitors
- apixaban (Eliquis) – oral tablets
- fondaparinux (Arixtra) - injection
- rivaroxaban (Xarelto) – oral tablets
- edoxaban (Savaysa) – oral coated tablets
Difference between Heparin and LMWH?
Both work w/ antithrombin to inactivate factor Xa, Unfractionated-heterogenous mixture of polysaccharide chains, inactivates Xa and IIa(thrombin) equaly
-5000U every 8-12hrs subQ
LMWH -fractionated natural heparin created by depolymerization, inactivates IIa to a lesser degree
-superior bioavailability and longer half life–> given once a day
Warfarin
- vit K dependent, many food and drug interactions
- slow acting
- monitor INR, PT time, INR 2-3= effective dose
- inhibits vitK reductase–> DEC in II, VII, IX, X, also protein C and S
- can take 5 days so need fast acting ar same time
What is fondaparinux (Arixtra) - injection?
factor Xa inhibitor, no effect on Thrombin
What reversal agents are available for DOAC?
Andexxa (Andexanet alfa) FDA approved for only Apixaban (Eliquis), Rivaroxaban (Xarelto) (factor Xa inhib)
Idarucizumab- for dabigatran (Pradaxa-direct thrombin inhib)
4F-PCC- prothrombin complex concentration
American College of Cardiology
https://www.acc.org/tools-and-practice-support/mobile-resources/features/manageanticoag
What is Tisseal?
Fibrin sealant, effective in heparinized patients
fibrinogen and thrombin which, upon mixing, mimics a physiological clot
aprotinin in TISSEEL increases resistance of the fibrin sealant clot to degradation in a fibrinolytic environment
-aprotinin-bovine pancreatic trypsin inhibitor (BPTI). Since it demonstrates the capacity to slow fibrinolysis
vWF Types
Quantitative Type 1 and 3
Qualitative Type 2, 2A, 2B, 2M, 2N
CBC
- RBC=(4.14-5.75 m/uL)
- Hgb=Males=12-18 g/ml; females= 12-16 g/ml.
- Hct % total bld vol made of RBC via centrifuge; M=40-54%; F=34-51%
- Mean Corpuscular Vol=79.7-97.6 fL; less than 80=microcytic anemia
- Mean Corpuscular Hgb= Hgb in RBC, 26.5-34.2 pg
- Mean Corpuscular Hgb Concentration: 32.9-35.5 g/dL, LO=iron DEF
- RDW- variation of RBC size= 12.6-15.2%
- WBC= 3.2-10.8 k/uL
- Platelet count=150,000 - 350,000/μL
Floseal
human thrombin and pre-filled sodium chloride syringe
gelatin granules and human thrombin to provide fast (2 min median time to hemostasis)
Gelfoam
purified pork Skin Gelatin USP Granules and Water for Injection, USP
-absorbed completely in 4-6 weeks
Oxtmetazoline (Afrin)
vasoconstrictor
Cryoprecipitate
1 unit= 10-20mL–> inc of 50mg/dL
Contains:
- Fibrinogen
- Factors VIII and XIII
- vWF
vWF
Synthesized in endothelial cells and megakaryocytes
necessary for adherence of PLTs to
exposed endothelium. vWF is a carrier
protein to F VIII:c and bound to it This
complex is part of the complete factor
VIII. Part of the intrinsic pathway:
includes factors 12, 11, 9, 5, 10, 2, 1.
vWF Disease tratment for bleeding
Autosomal Dominant
TX for bleeding: Desmopressin: 0.3mcg/kg 1-2 hr
prior to surgery.
Peaks: 30 min
Duration: 6-8 hrs.
Stimulates the release of vWF from the
endothelial cells increasing plasma
concentration of vWF. Inhances
fibrinolysis by causing the release of
tissue plasminogen activator. May need
to give ε-aminocaproic acid (plasmin
activator inhibitor) with the desmopressin
to help prevent plasmin from degrading
fibrinogen and fibrin.
Desmopressin causes fluid retention
If vWF 2b- NO DDAVP, will cause thrombocytopenia
When to transfuse?
hemoglobin (Hgb) is <7 to 8 g/dL(approximately equivalent to a hematocrit ≤21 to 24 percent) in most cardiac and noncardiac surgical patients
- and symptomatic
RBC: 1unit=350mL–> INC 1g/dL–>3% Hct
Prothrombin Plasma Concentrates versus Fresh Frozen Plasma
PPC indicated for fast reversal of supratherapeutic INR w/in 10min-dose of 25–50 units/kg
One dose of PCC equals 8 to 16 units of FFP
Advantages of PCC vs. FFP:10
- More effective and rapid correction of INR
- Greater increase in clotting factors
- Can be infused faster than FFP and with less volume
- Fewer complications secondary to fluid overload
- Shorter preparation time since PCC does not need to be thawed as FFP does
- Does not require blood-type matching
PCC contraindic in HIT
Types of PCC 4 vs 3 factor
Kcentra, 4 factor= 2, 7, 9, 10 in inactive forms
Bebulin and Profilnine, 3 factor= NO factor 7
also contains heparin to prevent activation of factors and also protein C and S
