Hematologic System Disorders

Hematologic System Disorders

Hematologic System Components

• Blood Vessel Wall

• White Blood Cell

• Red Blood Cell

• Platelets

• Blood Plasma

Hemostasis

• Five Stages of Hemostasis

  • Vessel spasm: Vasoconstriction

  • Formation of the platelet plug: Activation, adhesion, aggregation

  • Blood coagulation or development of an insoluble fibrin clot

  • Clot retraction: Joins the edges of vessel

  • Clot dissolution: Clot dissolves Fibrinolysis

Categories of Disorders of Hemostasis

• Thrombosis

  • The inappropriate formation of clots within the vascular system

• Bleeding

  • Failure of blood to clot in response to appropriate stimulus

Requirements for Blood Clotting Process

• Presence of platelets produced in the bone marrow

• Von Willebrand factor generated by the vessel endothelium

  • Required for adhesion

  • A carrier protein

• Clotting factors synthesized in the liver using vitamin K

Why Should Blood Clot?

• Hemostasis is designed to maintain the integrity of the vascular compartment.

• Related to:

  • Infection

  • Volume

  • Oxygen production

  • Tissue damage

  • Healing

Regulation of Blood Coagulation

• Antithrombin III:

  • Inactivates coagulation factors and neutralizes thrombin.

  • When complexed with naturally occurring heparin, its action is accelerated and provides protection against uncontrolled thrombus formation on the endothelial surface.

• Protein C:

  • A plasma protein that acts as an anticoagulant by inactivating factors V and VIII.

• Protein S:

  • Another plasma protein that accelerates the action of protein C.

• Plasmin:

  • Breaks down fibrin into fibrin degradation products that act as anticoagulants.

Hypercoagulability States

• Increase the risk of clot or thrombus formation in the arterial or venous circulations

• Arterial thrombi

  • Associated with conditions that produce turbulent blood flow and platelet adherence.

• Venous thrombi

  • Associated with conditions that cause stasis of blood flow with increased concentrations of coagulation factors.

Increased Platelet Function

• Hypercoagulability due to increased platelet function results in platelet adhesion, formation of platelet clots, and disruption of blood flow.

• The causes of increased platelet function are disturbances in flow, endothelial damage, and increased sensitivity of platelets to factors that cause adhesiveness and aggregation.

General Forms of Hypercoagulability States

• Conditions that create increased platelet function

  • Atherosclerosis

  • Diabetes mellitus

  • Smoking

  • Elevated blood lipoid and cholesterol levels

  • Increased platelet levels

• Conditions that cause accelerated activity of the coagulation system

  • Pregnancy and the puerperium

  • Use of oral contraceptives

  • Postsurgical state

  • Immobility

  • Congestive heart failure

  • Malignant diseases

Atherosclerotic Plaques and Platelets

• Smoking, elevated levels of blood lipids and cholesterol, hemodynamic stress, and diabetes mellitus predispose to vessel damage, platelet adherence, and eventual thrombosis.

• Platelets that adhere to the vessel wall release growth factors, which cause proliferation of smooth muscle and thereby contribute to the development of atherosclerosis.

• Atherosclerotic plaques disturb blood flow, causing endothelial damage and promoting platelet adherence.

Platelet Defects

• Thrombocytopenia

  • Results from a decrease in platelet production, increased sequestration of platelets in the spleen, or decreased platelet survival

  • Types

    • Drug-induced thrombocytopenia

    • Idiopathic thrombocytopenic purpura

    • Thrombotic thrombocytopenic purpura

• Impaired platelet function

Causes of Bleeding

• Decrease in the number of circulating platelets

  • Depletion of platelets must be relatively severe before hemorrhagic tendencies of spontaneous bleeding occur.

• Impaired platelet function

  • Bleeding resulting from platelet deficiency commonly occurs in small vessels and is characterized by petechiae and purpura.

Manifestations of Thrombocytopenia

• Bleeding

  • Mucous membranes

    • Nose, mouth, gastrointestinal tract, and uterine cavity

  • Commonly occurs in small vessels

• Petechiae—pinpoint purplish-red spots

  • Seen almost exclusively in conditions of platelet deficiency

• Purpura—purple areas of bruising

Thromboembolic Disease

• Results from a fixed (thrombus) or moving (embolus) clot that blocks flow within a vessel

  • Denies nutrients to tissues distal to the occlusion

  • Death can result when clots obstruct blood flow to the heart, brain, or lungs.

• Arterial thrombi: defects in proteins involved in hemostasis

• Venous thrombi: variety of clinical disorders or conditions

Thromboembolic Disease (Cont.)

• Treatment

  • Anticoagulants (heparin, coumadin)

  • Thrombolytic (streptokinase, urokinase)

• Virchow triad

  • Injury to the blood vessel endothelium: atherosclerosis, many others

  • Abnormalities of blood flow

  • Hypercoagulability of the blood

Thromboembolic Disease (Cont.)

• Hypercoagulability (thrombophilia)

  • Individual is at risk for thrombosis.

  • Primary (hereditary) vs. secondary (acquired)

    • Primary: defects in proteins that are involved in hemostasis.

    • Secondary: condition or disease that promote venous stasis.

  • Results from a deficiency of anticoagulation proteins.

Coagulation and Vitamin K

• Vitamin K is an essential cofactor for synthesis of clotting factors.

  • Fat-soluble vitamin synthesized by intestinal bacteria

  • In vitamin K deficiency, the liver produces inactive clotting factor resulting in abnormal bleeding.

Coagulation Defects

• Deficiencies can arise because of defective synthesis, inherited disease, or increased consumption of the clotting factors

• Hereditary disorders

  • Hemophilia A

  • Hemophilia B

  • Von Willebrand disease

  • Any genetic disruption of the production of clotting factor

Acquired Hypercoagulability

• Deficiencies in protein S and C and AT III

  • Contribute to a hypercoagulable state

• Antiphospholipid syndrome

  • Autoimmune syndrome characterized by autoantibodies against plasma membrane phospholipids and phospholipid-binding proteins

  • Treatment: heparin with aspirin

Hereditary Thrombophilias

• Inherited conditions increase risk for thrombosis.

  • Most are autosomal dominant.

Vascular Disorders that Cause Bleeding

• Hemorrhagic telangiectasia

  • An uncommon autosomal dominant disorder characterized by thin-walled, dilated capillaries and arterioles

• Vitamin C deficiency (scurvy)

  • Results in poor collagen synthesis and failure of the endothelial cells to be cemented together properly, causing a fragile wall

Vascular Disorders that Cause Bleeding (Cont)

• Cushing disease!

  • Causes protein wasting and loss of vessel tissue support because of excess cortisol

• Senile purpura (bruising in elderly persons)

  • Caused by the aging process

Disseminated Intravascular Coagulation

• Complex, acquired disorder: clotting and hemorrhage simultaneously occur

  • Sepsis, cancer or acute leukemia, trauma, blood transfusion

• Cause: variety of clinical conditions that release tissue factor

  • Causes an increase in fibrin and thrombin activity in the blood

  • Produces augmented clot formation and accelerated fibrinolysis

Disseminated Intravascular Coagulation (Cont.)

• Characterized by a cycle of intravascular clotting, followed by active bleeding

• Is caused by the initial consumption of coagulation factors and platelets

• Results from abnormally widespread and ongoing activation of clotting

• Hemorrhage: is secondary to the abnormally high consumption of clotting factors and platelets

• Deposition of fibrin clots in the circulation interferes with blood flow, causing widespread organ hypoperfusion

Disseminated Intravascular Coagulation (Cont.)

• Clinical manifestations demonstrate wide variability.

  • Bleeding from venipuncture sites

  • Bleeding from arterial lines

  • Bleeding from surgical wounds

  • Purpura, petechiae, and hematomas

  • Symmetric cyanosis of the fingers and toes

Signs and Symptoms of Disseminated Intravascular Coagulation

• Integumentary: petechiae, purpura, ecchymosis, pallor, oozing blood, venipuncture site bleeding, hematoma, occult hemorrhage, cyanosis, gangrene

• Respiratory: tachypnea, hemoptysis, orthopnea, decreased breath sounds, ARDS

• Cardiovascular: hypotension, tachycardia

• GI: hematemesis, occult bleeding/ bloody stools, abdominal distension/tenderness

• Urinary: oliguria/ anuria, hematuria

• Neurologic: dizziness, headache, changes in mental status, irritability, increased ICP, anxiety, stupor, coma

• MSK: bone & joint pain

Disseminated Intravascular Coagulation (Cont.)

• Treatment

  • Eliminate underlying pathology

  • Control thrombosis

  • Maintain organ function

  • Administer replacement therapy (transfusion)

  • Replace anticoagulants

Disorders of Coagulation

• Causes: defects or deficiencies of clotting factors

  • Vitamin K deficiency

  • Liver disease

  • Cardiovascular abnormalities

  • Vasculitis

  • Impaired hemostasis

Conditions Associated with Disseminated Intravascular Coagulation

• Obstetric conditions

• Cancers

• Infections

• Shock

• Trauma or surgery

• Hematologic conditions