Coagulation Modifiers Background

Goals of hemostasis

Maintain integrity of the vascular compartment

• prevent blood loss

Clotting factors released from injury activate and signal platelets to injury site leading to platelet plug formation

Primary hemostasis

Coagulation cascade causes formation of fibrin clot; results in stronger clot

Secondary hemostasis

Activation of plasmin leading to breakdown of clot when it is no longer needed

Clot lysis (fibrinolysis)

Primary hemostasis + coagulation Cascade steps (primary & secondary hemostasis)

Damaged blood vessel vasoconstrict (limit blood flow and triggers release of clotting factors that activate platelets and trigger coagulation cascade (prothrombin)

→

Prothrombin converted into thrombin; clotting factors activate platelets and signal them to site of injury 

→

Activated platelets forms a platelet plug; thrombin converts soluble fibrinogen into insoluble fibrin strands

→

Fibrin strands adhere to platelet plug to form an insoluble fibrin clot

What do endothelial cells do to maintain hemostasis?

• Vasoconstricts to minimize blood loss and release clotting factors

• Can also prevent thrombosis by producing anticoagulant factors

• Activate and aggregate at site of injury

• Lifespan is 7-10 days and removed by spleen

Platelets

What removes platelets?

Spleen

Intrinsic pathway of coagulation cascade (secondary hemostasis)

Occurs in vascular system

Extrinsic pathway of coagulation cascade (secondary hemostasis)

Occurs in the tissues

Normal platelet count

130,000 to 400,000 uL

Normal prothrombin (PT)

Measures viability of extrinsic pathway (tissue); normal is 10-13 sec

Normal activated partial thrombin time (aPTT)

Measures viability of intrinsic pathway (contact = vascular); normal is 28-38 sec

Normal fibrinogen (clot)

175 - 400 mg/dL

Normal D-dimer (measures fibrin breakdown; d-dimer is protein fragment made when clot dissolves)

<500 mg/mL

Conditions that would cause high d-dimer count

DVT, pulmonary embolism

Caused by damage to arterial endothelium which activates platelets

Arterial thrombus

Is associated with slow blood flow which allows thrombin/other procoagulants to concentrate and initiate coagulation cascade

Venous thrombus

Common causes of arterial thrombus

• Atherosclerotic plaque (inflammation attracts platelets)

• HTN

• Turbulent blood flow

Clinical manifestations of arterial thrombus

Obstructs blood flow

• Ischemia = decreased blood flow

• Infarction = tissue death

Common causes of venous thrombus

• Inactivity/prolonged bedrest

• Afib

Clot that caused by Afib

Venous thrombus

Clinical manifestations of venous thrombus

• Local congestion

  • edema, inflammation

• Embolism

  • Clot dislodges; easily detaches

  • S&S depends on where clot travels to and obstructs

Interventions to prevent arterial thrombus

Reduce CVD

• Low-fat, low-cholesterol diet

  • total cholesterol < 200 mg/dL

  • LDL < 130 mg/dL

• Weight reduction

• Control BP

• Avoid smoking/alcohol

• Reduce stress

• Regular exercise

Interventions to prevent venous thrombus

• Avoid tight clothing

• Avoid crossing your leg at the knees

• Minimize prolonged sitting or standing

• Bed rest

  • Perform ROM exercises

  • Wear compression stockings or SCDs (sequential compression devices)

• Road trips/traveling on a plane

  • Exercise your feet and legs

  • Ambulate if you can

Drugs that affect formation of the platelet plug

Antiplatelets

Treat arterial thrombus

Antiplatelet indication

Drugs that effect the coagulation cascade

Anticoagulants

Drugs that treat venous thrombus

Anticoagulant indication

Antiplatelets and anticoagulants break down existing clots. True or false?

False

Drugs that break down existing clots

Thrombolytics indication

Administer drug to treat massive bleeding/hemorrhaging; help prevent break down of clots in order to stop bleeding

Antifibrinolytics

High aPTT indicates

Takes longer to form clot → active/higher risk for bleeding