Chapter 2: Hematology Flashcards by Evan Adams

Three initial responses to vascular injury

Vascular vasoconstriction, platelet adhesion, thrombin generation

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Intrinsic coagulation cascade

Exposed collagen + prekallikrein + HMW kiniogen + Factor 12 -> activate factor 11 -> activate 9, then 8 -> activate 10, then add 5 -> Convert prothrombin (factor II) to thrombin -> thrombin then converts fibrinogen to fibrin

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Extrinsic coagulation cascade

Tissue factor (injured cells) + factor 7 -> activate 10, then add 5 -> convert prothrombin to thrombin -> thrombin then converts fibrinogen to fibrin

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Prothrombin complex (for intrinsic and extrinsic pathways)

10, 5, Ca, platelet factor 3, prothrombin.
Forms on platelets
Catalyzes the formation of thrombin

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Convergence point for intrinsic and extrinsic pathway

Factor 10

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Inhibits factor 10

Tissue factor pathway inhibitor

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Links platelets together (binds GpIIb /IIIa molecules) to form platelet plug -> hemostasis

Fibrin

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Helps crosslink fibrin

XIII

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Key to coagulation
Converts fibrinogen to fibrin and fibrin split products
Activates factors 5 and 13
Activates platelets

Thrombin

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Key to anticoagulation
Binds and inhibits thrombin
Inhibits factors 9, 10, and 11
Heparin activates AT-III (up to 1000x normal activity)

Antithrombin III (AT-III)

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Vitamin-K dependent; degrades factors 5 and 8; degrades fibrinogen

Protein C

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Vitamin K dependent, protein C cofactor

Protein S

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Released from endothelium and converts plasminogen to plasmin

Tissue plasminogen activator

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Degrades factors 5 and 9, fibrinogen, and fibrin -> lost platelet plug

Plasmin

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Natural inhibitor of plasmin, released from endothelium

Alpha-2 antiplasmin

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Components of fibrinolysis

Tissue plasminogen activator, plasmin, alpha-2 antiplasmin

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Factor: shortest half life

Factor 7

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Factors: labile factors, activity lost in stored blood; activity not lost in FFP

Factors 5 and 8

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Factors: only factor not synthesized in the liver (synthesized in the endothelium)

Factor 8

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Factors: 2, 7, 9, 10, protein C and protein S

Vitamin-K dependent factors

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Takes 6 hours to have effect

Vitamin K

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Effect is immediate and lasts 6 hours

FFP

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Prothrombin

Factor II

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Half life: RBCs

120 days

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Half-life: platelets

7 days

Half life: PMNs

1-2 days

- From endothelium | - Decreases platelet aggregation and promotes vasodilation (antagonistic to TXA2)

Prostacyclin (PGI2)

- From platelets - Increases platelet aggregation and promotes vasoconstriction - Triggers release of calcium in platelets -> exposes Gp2b/3a receptor and causes platelet-to-platelet binding; platelet-to-collagen binding also occurs (Gp1b receptor)

Thromboxane (TXA2)

Contains highest concentration of vWF-VIII; used in von Willebrand's disease and hemophilia A (factor 8 deficiency), also has high levels of fibrinogen

Cryoprecipitate

Has high levels of all coagulation factors, protein C, protein S, and AT-III

FFP

Causes release of VIII and vWF from endothelium

DDAVP and conjugated estrogens

Measures 2, 5, 7, and 10; fibrinogen; best for liver synthetic function

Measures most factors except 7 and 13 (thus does not pick up factor 7 deficiency); also measures fibrinogen

PTT

What do you want PTT for routine anticoagulation?

60 - 90 sec

ACT

activated clotting time

What do you want ACT (activated clotting time) for routine anticoagulation?

Want ACT 150 - 200 sec for routine anticoagulation, > 460 sec for cardiopulmonary bypass

INR: relative contraindication to performing routine procedures

INR > 1.5

INR: relative contraindication to central line placement, percutaneous needle biopsies, and eye surgery

INR > 1.3

Most common cause of surgical bleeding

Incomplete hemostasis

Most common congenital bleeding disorder

Von Willebrand's disease

- Reduced quantity of vWF | Tx: recombinant VIII:vWF, DDAVP, cryoprecipitate

Type 1 von Willebrand's disease

- Defect in vWF molecule itself, vWF does not work well | Tx: recombinant VIII:vWF, cryoprecipitate

Type 2 von Willebrand's disease

- Complete vWF deficiency (rare) | Tx: recombinant VIII:vWF, cryoprecipitate; (DDAVP will not work)

Type 3 von Willebrand's disease

Lab findings of von Willebrand's disease

PT normal; PTT can be normal or abnormal. Prolonged bleeding time (ristocetin test).

- VIII deficiency - Sex linked recessive - Prolonged PTT, normal PT

Hemophilia A

Why may hemophilia A newborns not bleed at circumcision?

Factor 8 crosses the placenta

Treatment for hemophiliac joint bleeding

- Do not aspirate - Ice, keep joint mobile with ROM exercises - Factor 8 concentrate or cryoprecipitate

Treatment for hemophiliac epistaxis, intracerebral hemorrhage, or hematuria

Recombinant factor 8 or cryoprecipitate

Goals for hemophilia A pre and post op

Need levels 100% pre-op, keep at 80-100% for 10-14 days after surgery

- Sex-linked recessive - Prolonged PTT and normal PT Tx: Recombinant factor 9 or FFP

Hemophilia B - Factor 9 deficiency - Christmas Disease

Goals for Hemophilia B pre and post op

Need levels 100% pre-op, keep at 30-40% for 2-3 days after surgery

Prolonged PT. Normal PTT. Bleeding tendency. Tx: Recombinant factor 7 concentrate or FFP

Factor 7 deficiency.

Causes bruising, epistaxis, mucosal bleeding, petechiae, purpura.

Platelet disorders

Platelet disorder: caused by H2 blockers, heparin

Acquired thrombocytopenia

Platelet disorder: Gp2b/3a receptor deficiency on platelets (cannot bind to each other). - Fibrin normally links the Gp1b/3a receptors together. Tx: ?

Glanzmann's thrombocytopenia | Tx: Platelets

Gp1b receptor deficiency on platelets (cannot bind to collagen) - vWF normally links Gp1b collagen. Tx: ?

Bernard Soulier | Tx: Platelets

How does uremia affect platelets?

Uremia inhibits platelet function. | Tx: hemodialysis (1st), DDAVP, platelets

Thrombocytopenia due to antiplatlet antibodies (IgG PF4 antibody) results in platelet destruction. - Can also cause platelet aggregation and thrombosis. - Forms a white clot. - Can occur with low doses of heparin.

Heparin-induced thrombocytopenia (HIT)

Treatment for heparin-induced thrombocytopenia (HIT)

Stop heparin, start argatroban (direct thrombin inhibitor) to anticoagulate

- Decreased platelets, low fibrinogen, high fibrin split products, and high d-dimer - Prolonged PT and prolonged PTT - Often initiated by tissue factor Tx: need to treat the underlying cause

Disseminated intravascular coagulation (DIC)

Inhibits cyclooxygenase in platelets and decreases TXA2

Aspirin

Aspirin pre-op recommendations

Stop 7 days before surgery; patients will have prolonged bleeding time

Plavix pre-op recommendations

Stop 7 days before surgery; ADP receptor antagonist. | Tx: platelets

Coumadin pre-op recommendations

Stop 7 days before surgery; consider starting heparin while Coumadin wears off

Platelet pre-op recommendations

Want them > 50,000 before surgery, > 20,000 after surgery

Surgery: can release urokinase, activates plasminogen -> thrombolysis. Tx: e-aminocapropic acid (Amicar)

Prostate surgery

Best way to predict bleeding risk

H & P

Does normal circumcision rule out bleeding disorders?

No, they can still have clotting factors from the mother

Picks up 99% of patients with bleeding disorder

Abnormal bleeding with tooth extraction or tonsillectomy

Common with vWF deficiency and platelet disorders

Epistaxis

Common with bleeding disorders

Menorrhagia

Present as venous or arterial thrombosis / emboli (e.g., DVT, PE, stroke)

Hypercoaguability Disorders

- 30% of spontaneous venous thromboses - MC congenital hypercoaguability disorder. - Causes resistance to activated protein C; the defect is on factor 5. Tx: heparin, warfarin

Factor V Leiden mutation

Treatment for hyperhomocysteinemia

Folic Acid. | B12

Tx: prothrombin gene defect G20210A

Heparin, warfarin

Tx: protein C or S deficiency

Heparin, warfarin

- Heparin does not work in these patients - Can develop after previous heparin exposure Tx: recombinant AT-III concentrate or FFP (highest concentration of AT-III) followed by heparin, then warfarin

Antithrombin H1 deficiency

Tx: dysfibrinogenemia, dysplasminogenemia

Heparin, warfarin

- Defect in platelet function; can get thrombosis | - Keep Hct

Polycythemia vera

Causes of polycythemia vera

Primary: JAK2 mutation Secondary: low oxygen tension (e.g.: living at high altitudes, smoking, carbon monoxide exposure)

- Procoagulant (get prolonged PTT, but are hyper coagulable) | - Caused by antibodies to cardiolipin and lupus anticoagulant (phospholipids)

Anti-phospholipid antibody syndrome)

``` Prolonged PTT (not corrected with FFP). Positive Russell viper venom time, false-positive RPR test for syphillis. Tx: heparin, warfarin ```

Anti-phospholipid antibody syndrome

MC factor causing acquired hypercoagulability

Tobacco

Causes of acquired hyper coagulability

Tobacco. Malignancy. Inflammatory states. IBD. Infections. OCPs. Pregnancy. Rheumatoid arthritis. Post-op patients. Myeloproliferative disorders.

How does cardiopulmonary bypass result in hyper coagulability?

Activates Factor 12 (Hageman factor). Tx: heparin to prevent.

Why does warfarin-induced skin necrosis occur?

Short half-life of proteins C and S, which are first to decrease in levels compared with the pro coagulation factors; results in relative hyperthrombotic state. - Occurs when placed on coumadin without being heparinized first.

Who is at risk for warfarin-induced skin necrosis?

Patients with relative protein C deficiency are especially susceptible.

Key elements in the development of venous thromboses

Virchow's triad (stasis, endothelial injury, hyper coagulability)

Key element in the development of arterial thrombosis

Endothelial injury

Risk factors for DVT

Stasis. Venous injury. Hypercoaguability.

Post-op DVT Tx: 1st: 2nd: 3rd:

1st: Warfarin for 6 mo. 2nd: Warfarin for 1 yr. 3rd or significant PE: Warfarin for life.

Indications for Greenfield filter

- Contraindications to anticoagulation - Documented PE while on anticoagulation - Free-floating IVC, ilio-femoral, or deep femoral DVT - Recent pulmonary embolectomy

When are temporary IVC filters indicated?

Can be inserted in patients at high risk for DVT (e.g. head injury patients on prolonged bed rest)

Most common origin of PE

Ilio-femoral region

Tx pulmonary embolism

Shock (despite massive interpose, pressors) -> OR. | No shock -> Heparin (thrombolytics have not shown an improvement in survival) or suction catheter-based intervention.

- Inhibits fibrinolysis by inhibiting plasmin | - Used in DIC, persistent bleeding following cardiopulmonary bypass, thrombolytic overdoses

Aminocaproic acid (Amicar)

Prevents vitamin-K dependent decarboxylation of glutamic residues on vitamin K dependent factors

Warfarin

Improve venous return but also induce fibrinolysis with compression (release of tPA (tissue plasminogen activator) from endothelium.

SCDs.

- Binds and activates anti-thrombin III - Reverse with protamine - Cleared by the reticuloendotehlial system - Does not cross placental barrier

Heparin

Risks of long-term heparin

Osteoporsis. Alopecia.

Half-life / goal PTT of heparin

Half-life: 60-90 minutes. | Goal PTT: 60-90 seconds

Cross reacts with NPH insulin or previous protamine exposure; 1% get protamine reaction (hypotension, bradycardia, and decreased heart function).

Protamine

- Lower risk of HIT compared to unfractionated heparin - Binds and activates antithrombin III but increases neutralization of just 10a and thrombin - Not reversed with protamine

Low molecular weight heparin (ex, enoxaparin, fondaparinux)

- Reversible direct thrombin inhibitor - Metabolized in the liver - Half life: 50 minutes - Often used in patients with HITT

Argatroban

- Reversible direct thrombin inhibitor - Metabolized by proteinase enzymes in the blood - Half life: 25 minutes

Bivalirudin (Angiomax)

- Irreversible direct thrombin inhibitor - Most potent direct inhibitor or thrombin - High risk for bleeding complications

Hirudin (Hirulog; form leeches)

Malayan pit viper venom; stimulates tPA release

Ancrod

- Activate plasminogen | - Need to follow fibrinogen levels: fibrinogen

Thrombolytics: Streptokinase, urokinase, tPA

Treatment for thrombolytic overdose

e-aminocaproic acid (Amicar)

Absolute contraindications to TPA

Active internal bleeding. Recent CVA or neurosurgery (

Major contraindications to TPA.

Recent (

Minor contraindications to TPA.

Minor surgery. Recent CPR. A fib with MV disease. Bacterial endocarditis. Hemostatic defects (i.e. renal or liver disease). Diabetic hemorrhage retinopathy. Pregnancy.

Chapter 2: Hematology Flashcards

(112 cards)