Blood: Coagulation Flashcards by Aisha Abdulhakeem

Mechanism of coagulation

Vasospasm
Platelet functions
Plug reinforcement by fibrin
Fibrin triggers plasmin formation from plasminogen through t PA

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Platelet functions:

Platelet stick to exposed collagen and vWf
Then adhere to each other
Then aggregate and become activated
Activated platelet release ADP (change platelet shape, enhance aggregation and generate TXA2)
Releas serotonin for VC
Release TXA2 fir more aggregation
Activated platelets express receptors for vWf, fibrinogen and collagen and clotting protein thrombin
Then form platelet plug

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Plasmin…

Splits fibrin and fibrinogen into fragments interfering with thrombin activity, platelet function and fibrin polymerization dissolving the clot

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White thrombus

In arteries due to platelet adhesion after high pressure circulation land vessel injury

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White thrombus risk factors

Smoking
HT
Hyperlipidemia
DM
Chol. emboli from all sorts of thrombosis

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Red thrombus

In veins due to stasis triggering fibrin network enmeshed with RBCs

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Red thrombus risk factors

Pregnancy
Post child birth period
Oral contraceptives or estrogen replacement therapy
High corticos
Immobilisation or bone fracture
Knee hip abdominal surgery
Catheters

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Increase in size of red thrombus

Forms a long tail that cuts off forming an emboli

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Coagulation cascade

Intrinsic and extrinsic

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Intrinsic

12 to 11 to 9 to 10

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Etrinsic

7 plus Tissue factor? to 10

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Factor 10 activates

Prothrombin (2) complex so thrombin (2a) is formed
Activates 13
Plus activated fibrinogen
Then clot

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Endogenous anticoagulants

Protein C and S kill factors Va and VIIIa
Antithrombin III inactivates 7 9 10 and 12
The fibrinolytic system including plasmin, plasminogen and tPA that limits dissemination of coagulation by inhibiting escape of coagulation proteins ousmtside the area of the injury

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Anticoagulants

In vitro - precipitate or remove Ca from blood like EDTA and sodium oxalate
In vivo and vitro - paranteral
In vivo only - oral

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Patanteral

Direct and indirect

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Indirect thrombin inhibitors

Unfractionated (HMW)
LMWH
Fondaparinux

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Direct thrombin inhibitors (heparin like)

Lepirudin
Bivalirudin
Argatroban

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Sulfated mucopolysaccharide that’s a strong acid with negative charge

HMWH

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Not effective orally

Its negative charge and HMW doesn’t allow it to be absorbed from the gut
So taken paranterally - Heparin

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Never IM

Heparin as it causes hematoma and has an unpredictable absorption rate

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Partly excreted unchanged in urine

As uroheparin

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Allowed in pregnancy and lactation

As it doesn’t cross placenta and isn’t secreted in milk

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Onset of heparin action

Immediate with IV and delayed 20 to 60 minutes SC

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Heparin liberates

Lipoprotein lipase which helps in lipemia

Indirect effect of heparin

Kn antithrombin 3 to inhibit factors 2 and 10

Heparin doses

Initial - 5000 to 10 000 Maintenance - 75 to 100 Prophylaxis - 5000

Control of heparin dose with

Activated thromboplastin time not exceeding 2 - 2.5 times the normal Clothing time to be 2 - 2.5 times the normal Anti factor 10 activity

Normal thromboplastin time

26 - 33

Antidote of heparin excess

Fresh blood Protamine sulphate as is a string base and carries strong positive charge However, excess protamine is bad as it's also an anticoagulant

Uses of heparin

-Treatment of deep vein thrombosis plys pulmonary embolisms plus MI plus cerebral thrombosis -Prophylaxisof postoperative thrombosis and embolism Prevention of blood clotting during disgusting and in dialysis machines

Side effect of any anticoagulant

Bleeding

Heparin induced thrombocytopenia

Treated by discontinuation of heparin So platelet number immune response decrease is gone And administration of direct thrombin inhibitors to reduce the Venous and arterial embolisms

Heparin inhibits aldosterone synthesis

So side effect is hyperkalemia

Drugs that potentiate heparin - probleeding drugs

Other anticoagulants, aspirin, clopidorgel, warfarin and NSAIDs like ibuprofen, naproxen, diclofenac

Transient alopecia and osteoporosis

Heparin side effect

Drugs that decrease heparin

Digitalis Tetracycline Nicotine Antihistamines IV nitroglycerin

Heparin contraindicated in

Liver and Kidney disease s because metabolism and excretion

Bleeding disorders contraindications

Hemophilia Intracranial hemorrhage Visceral carcinoma

Other heparin contraindications

Surgery- eye brain spine Active TB, ulvmcerative gut and subacute bacterial endocarditis HT and intracranial hemorrhage Heparin induced thrombocytopenia patients

LMWH

Enoxaparin Dalteparin Tinzaparin

LMWH produced from

Chemical or enzymatic depolarization of HMWH and weigh 5000 Dalton

Mechanism of LMWH

Potentiate antithrombin 3 with special action on factor 10

No complete neutralisation by protamine sulphate

LMWH

Why L and not HMWH

Taken SC Longer half lives so take once or twice No need for lab monitoring as they are predictable (pharmacokinetics and dynamics), they don't bind to macrophages or platelets and all so no risk of thrombocytopenia

More reasons L and not HMWH

Less hemorrhage Moreeffective and safer(more selective) Anti factor 10a assays good- therapeutic is 0.5 to 1.2 and prophylactic is 0.2 to 0.5

No need to emaseur LMWHexcept in

Renal insufficiency Obesity Pregnancy

Fondaparinux - the best so far

Same mechanism One dose (long 15hrs half life) SC Greater than LMW at thromboembolism prophylaxis Bleeding side effect with no antidote but fresh blood (not heparin like the rest so kritamine sulphate doesn't work on it)

Only contraindication of Fondaparinux is

Severe renal impairment

Paranteral - Direct Thrombin Inhibitors

Directly binding to thrombin, inhibiting it SC and IV

Lepirudin

Take it when you have heparin induced thrombocytopenia and you need an anticoagulant

Bivalirudin

With unstable angina and undergoing coronary angioplasty

Argatrobin

H Induced Thrombocytopenia with or without thrombosis and coronary angioplasty

Short half life DTI- IV

Bivalirudin and Argatroban

Monitored by aPTT

Argatroban

Dose reduction of Argatroban with

Liver impairment

High International Normalized Ration in

Argatroban patients making transition to Warfarin difficult

Oral anticoagulants - vit.K antagonist Warfarin