HEMOSTASIS

HEMOSTASIS

is a complex process involving multiple steps and many clotting factors.

HEMOSTASIS

is the balance between clot formation and clot breakdown

1. Vascular Phase

2. Platelet Phase

3. Coagulation Phase

4. Clot formation

5. Fibrinolysis

Steps in Hemostasis

Vascular phase

Cutting or damaging blood vessels leads to vascular spasm that produces a vasoconstriction which will slow or even stop blood flow.

Platelet phase

In larger blood vessels, platelets begin to stick to the surfaces of endothelial cells.

Aggregation of platelets leads to the formation of a platelet plug

Coagulation phase

The overall process involves the formation of the insoluble protein Fibrin from the plasma protein Fibrinogen through the action of the enzyme Thrombin. Fibrin forms a network of fibers which traps blood cells and platelets forming a thrombus or clot.

Thrombin

Enzyme responsible for making of Fibrinogen to Fibrin

Fibrin

forms a network of fibers which traps blood cells and platelets forming a thrombus or clot.

Thrombus/clot

Fibrin forms a network of fibers which traps blood cells and platelets forming a

Extrinsic & Intrinsic pathway

Two pathways leading to the

formation of the thrombus:

Extrinsic pathway

Initiated with material outside of the blood.

Extrinsic pathway

• Very rapid process

• Smaller clots

Intrinsic pathway

Initiated by the blood coming in contact with exposed collagen in the blood vessel wall

Intrinsic pathway

• Slower

• Larger clots

Extrinsic pathway

factor Vlla, tissue factor

Intrinsic pathway

Factir Vllla, lXa, Xla

Calcium, phospholipid

Prothrombinase complex

Factor Va, X, cal

Clot Retraction

After 2 or 3 days, the clot begins to contract. Platelets in the clot contain contractile proteins.

contractile proteins

In Clot Retraction the clot begins to contract. Platelets in the clot contain

contractile proteins.

These proteins pull the edges of the wound together and reduces the chance of further hemorrhage. This activity also assists the repair processes.

Fibrinolysis

Dissolution of the clot.

Plasmin.

In Fibrinolysis the breakdown of the clot is due to the production of a powerful proteolytic enzyme

Fibrinolysis

Removing a blood clot is essential to restoring normal circulation.

Fibrinolysis

This step complete the HEMOSTASIS

stationary clot forms (thrombus)

it often grows larger as more fibrin is added.

embolus

▪Pieces of the clot may break off and travel in the blood stream to possibly lodge elsewhere.

▪A traveling clot is know as an

Anticoagulants

used to prevent the formation of clots

Antiplatelets

used to inhibit platelet aggregation

Thrombolytics

used to dissolve such life-threatening clots

Hemostatics

used to speed clot formation, or to limit bleeding from a surgical site

Anticoagulants

Antiplatelets

Thrombolytics

Hemostatics

DRUGS FOR Coagulative & BLEEDING DISORDER

ANTICOAGULANTS

prevent the formation and enlargement of clots.

Enoxaparin (Lovenox)

Tinzaparin (Innohep)

Dalteparin (Fragmin)

LMWH example

ANTICOAGULANTS

ACTIONS:

1) Inhibit certain clotting factors

2) Lengthen clotting time

3) Prevent thrombi from forming or growing larger

Coumarin

Chemistry of Warfarin

Sulfated glycosaminoglycan

Chemistry of Heparin

WARFARIN MOA

Inhibits vitamin K synthesis

HEPARIN MOA

Activates antithrombin III

WARFARIN

Route Oral or IV

HEPARIN

Route IV or SC

Hematoma

HEPARIN when administered IM causes

PT-INR

WARFARIN monitoring

aPTT

Heparin monitoring

Warfarin

Target INR 2-3

Heparin

Target 1.5-2.5x control

WARFARIN

Prophylactic for acute MI, prevention of progression or recurrence of acute deep-vein thrombosis or pulmonary embolism

Bleeding, Teratogenic

WARFARIN side effects

Vitamin K

Antidote for WARFARIN

HEPARIN

prevention of venous thrombosis, tx of pulmonary embolism and acute myocardial infarction

Bleeding, allergy, thrombocytopenia

HEPARIN side effecfs

Protamine SO4

Antidote for HEPARIN

VITAMIN K

A procoagulant used as antidote for Warfarin toxicity.

Enoxaparin (Lovenox)

Tinzaparin (Innohep)

Dalteparin (Fragmin)

LOW MOLECULAR WEIGHT HEPARIN (LMWH)

DRUGS:

(Lovenox)

Enoxaparin BN

Innohep

Tinzaparin BN 

Fragmin

Dalteparin BN

LOW MOLECULAR WEIGHT HEPARIN (LMWH)

anticoagulants of choice for treating pregnant women with prosthetic heart valves or venous thromboembolism

LOW MOLECULAR WEIGHT HEPARIN (LMWH)

• Do not require intense monitoring

• Longer half-life than heparin

• With less bleeding

Fondaparinux

is a small synthetic drug that contains the biologically active pentasaccharide present in unfractionated and LMW heparins

LMWH

Fondaparinux

LEPIRUDIN

ARGATROBAN

Dabigatran

DIRECT THROMBIN INHIBITORS

Oral

DABIGATRAN route

LEPIRUDIN

Polypeptide that is closely related to hirudin

LEPIRUDIN

effective in the treatment of HIT

streptokinase or alteplase

LEPIRUDIN CI

Liver

Clotting factor produced in the

Thromboxane A2

Adenosine diphosphate

Serotonin

Platelet aggregations factor

Thromboplastin/factor 3

The platelet aggregation that plug together releases an important factor which is the platelet…

which then activates the clotting coagulation

Platelet adhesion, Platelet aggregation

Vascular phase aka

Coagulation cascade

Coagulation phase aka

Prothrombinase

Responsible enzymes to convert prothrombin to thrombin

Unfractionated haparin

LMWH

2 types of heparin