Hemostasis and Coagulation Processes

Hemostasis

• Hemostasis is a series of events that stops bleeding from damaged blood vessels, maintaining blood flow to all body tissues.
• It depends on the integrity of blood vessels, platelets, and coagulation factors.
• Hemostatic abnormalities can cause excessive bleeding or thrombosis.

Normal Hemostasis

• Normal hemostasis involves regulated processes that keep blood fluid and clot-free in healthy vessels while rapidly forming a localized hemostatic plug at the site of vascular injury.

Pathologic Counterpart

• The pathologic counterpart of hemostasis is thrombosis, the formation of a blood clot (thrombus) within intact blood vessels.

Coagulation Cascade

• The coagulation cascade is a series of enzymatic conversions.
• Inactive proenzymes are turned into activated enzymes.
• This process culminates in thrombin formation, which converts fibrinogen to fibrin, strengthening the clot.

Steps in Hemostasis

• Hemostasis involves the formation of a primary platelet plug due to platelet adhesion to collagen.
• The plug converts into a permanent plug supported by fibrin.

Pathways of Hemostasis

• Hemostasis occurs through two pathways: intrinsic and extrinsic.
• The extrinsic pathway is initiated by tissue factor (TF), while the intrinsic pathway is triggered by factors in the blood.
• Both pathways converge to activate Factor X, which then activates prothrombin to thrombin.

Laboratory Tests for Bleeding Abnormalities

• Platelet count
• Partial thromboplastin time (PTT)
• Prothrombin time (PT)
• Thrombin time (TT)

Partial Thromboplastin Time (PTT)

• This test screens the activity of proteins in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, and fibrinogen).
• Clot formation time is typically 28–35 seconds.

Prothrombin Time (PT)

• This test screens the proteins in the extrinsic pathway (factors VII, X, II, V, and fibrinogen).
• Fibrin clot formation time is usually 11–13 seconds.

Thrombin Time (TT)

• This test assesses fibrin formation from fibrinogen in plasma.
• The reference range is usually less than 20 seconds (15–19 seconds).

Thrombus

• A thrombus is a blood clot composed of platelets, fibrin, erythrocytes, and leukocytes.
• Thrombi can form anywhere in the circulatory system.

Virchow's Triad

• Three conditions promote thrombus formation: endothelial injury, sluggish blood flow, and increased coagulopathy.

Conditions Associated with DVT

• Conditions associated with deep vein thrombosis (DVT) include cancers, advanced age, prolonged bed rest, postoperative periods, late pregnancy, and postpartum periods.

Embolus

• Thrombus formation results in several possible outcomes: dissolution, occlusion of a blood vessel, recanalization, or embolus development.
• An embolus occurs when a portion or all of a thrombus breaks away and travels through the circulatory system, potentially becoming lodged in a smaller vessel.

Diseases of the Platelets

• Platelets are vital components of the clotting process.
• Normal platelet levels range from 150,000 to 350,000 cells/mL.
• Thrombocytosis (increased platelet levels) increases the risk of thrombus formation.
• Thrombocytopenia (decreased platelet levels) increases the risk of bleeding.
• Platelet disorders involve abnormalities in quantity or quality of platelets.

Hemophilia A

• Hemophilia A is an X-linked recessive bleeding disorder.
• Characterized by a deficiency or abnormality in clotting factor VIII.
• Severity varies based on factor VIII levels in the blood.
• Bleeding is the main symptom.
• Treatment involves replacing clotting factors through transfusions.

Von Willebrand's Disease

• Most common hereditary bleeding disorder.
• Results from a deficiency of von Willebrand factor.
• Clinical manifestations are characterized by abnormal bleeding.

Disseminated Intravascular Coagulation (DIC)

• Life-threatening condition that occurs as a complication of other diseases, such as serious infections or injuries.
• During injury, clotting factors are activated and travel to the injury site to stop bleeding.
• In DIC, these clotting factors become abnormally active, leading to excessive clot formation in small blood vessels.
• Consequently, small clots can occlude blood supply to tissues and organs.
• Over time, clotting factors are consumed.
• Symptoms include tissue and organ ischemia (reduced blood supply) and abnormal bleeding.
• Management focuses on identifying and treating the underlying cause and replacing platelets and clotting factors to control bleeding.

Immune Thrombocytopenic Purpura (ITP)

• Immune system destroys its own platelets.
• Circulating immunoglobulin G antibodies react with platelets, leading to their destruction in the spleen and liver.
• Acute ITP is more common in children.
• Chronic ITP is more common in adults (aged 20–50) and women.
• Abnormal bleeding is the primary clinical manifestation.

Thrombotic Thrombocytopenic Purpura (TTP)

• Deficiency of the enzyme ADAMTS13, which is needed to cleave (inactivate) von Willebrand factor.
• This deficiency leads to increased clotting, and available platelets decrease.
• TTP is characterized by thrombi, thrombocytopenia, and bleeding.

Venous Thrombosis

• Can occur in superficial or deep veins of the legs.
• Superficial vein thrombosis (occurs when varicosities are present). Symptoms include local congestion, swelling, pain, tenderness, and possible overlying skin infections.
• Deep vein thrombosis (DVT) is more serious, potentially leading to pulmonary emboli (blood clots in the lungs). Symptoms usually include edema, pain, and tenderness.

Deep Venous Thrombosis (DVT)

• DVT occurs with stasis (slowing) in venous circulation (e.g., heart failure, sedentary lifestyle).
• Conditions associated with DVT include cancers, advanced age, prolonged bed rest, postoperative periods, late pregnancy, and postpartum periods.