Bleeding & Clotting Disorders

By

Dr. Sumaira Iqbal

LEARNING OBJECTIVES

• By the end of lecture student should be able to

• Comment on physiological basis of bleeding, platelet and coagulation disorder including hemophilia and thromoboembolic diseases

• Relate Coagulation profile with disorders

Bleeding disorders

• Vessel wall disorder

• Platelet disorder

• Congenital coagulation disorders

– Hemophilia A

– Hemophilia B

– Von Willibrand’s Disease

VESSEL WALL DISORDER

SCURVY• Vitamin C Deficiency

• Vit C level falls below 10mg/d

• Essential for synthesis of collagen.

• Hemorrhage in muscles , joints , nail beds & gingival tissues.

VESSEL WALL DISORDER

• GINGIVITIS PRESENTATION– Swelling

– Friability

– Bleeding

– Secondary infection

– Loosening of teeth

• Treatment:– Diet rich in Vitamin C

– Administration of 1g/d of Vitamin C supplements

PLATELET DISORDERS

• CONGENITAL

• ACQUIRED

THROMBOCYTOPENIA

• Quantity of platelets when reduced by

– Decreased production in the bone marrow

– Increased sequestration in the spleen

– Accelerated destruction

TREATMENT: Platelet Transfusion.

PLATELET DISORDERS

THROMBOCYTOPENIA

Causes:

• Drug induced like ASPIRIN

• Bone marrow failure

• Hypersplenism

• Idiopathic

• Lymphomas

• Aplastic anemia

PLATELET DISORDERS

THROMBOCYTOPATHIES

Qualitative defects in platelet ADHESION, AGGREGATION, RELEASE OF COAGULATION FACTORS,

Conditions like

Glanzman’s Thrombasthenia

Bernard soulier syndrome

PRESENTATION

• Skin purpura

• Superficial bruising

• Epistaxis

• Menorrhagia

• Mucosal hemorrhage is seen in severe cases and intra-cranial hemorrhage is rare.

IDIOPATHIC THROMBOCYTOPENIA• Caused by accelerated antibody mediated platelet

destruction

• CAUSE: not known

• Oral hematomas & hemorrhagic bullae may occur

• Intracanial hemorrhage is the most common cause of death

• TREATMENT

– Blood transfusion

– Splenectomy

– Corticosteroids

COAGULATION DISORDER

• Disorders of formation and activation

• Decreased formation --- Liver diseases like

– Cirrhosis of liver

– Hepatitis

– Yellow atrophy

• Vitamin K deficiency

– Activates II, VII, IX, X and protein C

COAGULATION DISORDER

• Vit-K ----- liver carboxylase

– Add carboxyl group to glutamic acid residue

– Vitamin K becomes oxidized and inactive

– Vitamin K epoxide reductase bring back it to reduced and active form

• Synthesized in intestines

• Deficiency is rare in adults

• Deficiency results from poor absorption of fats

• May occur due to inappropriate bile secretion

HEMOPHILIA

• Deficiency of Factor VIII (Antihaemophilic factor)

• Also known as classic hemophilia

• Inherited as an X – linked trait.

• 10 times more commonly than hemophilia–B

• In 85% cases hemophilia is due to deficiency of factor VIII

• In 15% cases hemophilia is due to deficiency of factor IX

HEMOPHILIA

CLINICAL FEATURES

• No racial predilection• AGE-Bleeding manifestations begin after 6

months of age• SIGNS:

– Hematomas,– Hemarthroses– Hematuria– GI bleeding– Bleeding from laceration– Spontaneous intra cranial bleeding

HEMOPHILIA

• TREATMENT

– Factor VIII concentrates

VON WILLEBRAND’S DISEASE

• Deficiency of VWF & amount of Factor VIII

• Von Willebrand factor

– Synthesis in endothelium and megakaryocytes

– Smaller component of factor VIII

– Anchors platelets to subendothelium

– Bridge between platelets

• Inheritance - autosomal dominant

• Incidence - 1/10,000

• Clinical features – similar to hemophilia

CHRISTMAS DISEASE

• Hereditary deficiency of factor IX.

• Inherited as X – linked recessive trait

• Very rare compared to Hemophilia-A

• Clinical presentation same as Hemophilia A

• TREATMENT:

Recombinant factor IX

THROMBOEMBOLIC CONDITIONS

THROMBOEMBOLIC CONDITIONS

• THROMBOSIS

“Pathological formation of hemostatic plug within the vasculature (in vivo) in the absence of bleeding”

• EMBOLUS

“Detachment of clot from the actual site and flow freely in blood”

THROMBOEMBOLIC CONDITIONS

• Thromboembolic conditions

• Conditions favour thrombus formation

– Rough endothelial surface

(Atherosclerosis, infection or trauma)

– Sluggish blood flow

(Polycythemia or CHF)

• Disseminated intravascular coagulation

– Septicemia

• Emboli that originate from large arteries or in the left side of heart plug small arteries or arterioles of brain and kidneys.

• While emboli originate from venous system or right side of heart plug pulmonary arteries.

Disseminated Intravascular Coagulation

• Clotting mechanism is activated in widespread areas of circulation

• Presence of large amount of traumatized that release great quantity of tissue factor into blood

• Also seen in septicemia in which bacterial endotoxins activate clotting mechanism

• Plugging of small vessels leads to inefficient nutrient and oxygen provision

• Lack of blood flow

Systemic activation

of coagulation

Intravascular

deposition of fibrinDepletion of platelets

and coagulation factors

BleedingThrombosis of small

and midsize vessels

with organ failure

Disseminated Intravascular Coagulation

• Diagnosis

–FDPs raised

• Treatment

– Treatment of underlying disorder

– Anticoagulation with heparin

– Platelet transfusion

BLOOD COAGULATION TESTS

Coagulation profile

• Bleeding time

• Clotting time

• Prothrombin time

• INR

Bleeding Time (BT)

is the time interval between the skin puncture and spontaneous, unassisted (i.e. without pressure)

stoppage of bleeding. The BT test is an in vitro test of platelet function.

• 1-5 minutes

• Prolonged in thrombocytopenia (primary)

• Normal in clotting disorders

Clotting time (CT)

is the time interval between the entry of blood into the glass capillary tube, or a syringe, and

formation of fibrin threads

• 2 – 4 minutes

• Give the information of clotting factors

Prothrombin time

Measures the time required for fibrin clot to form when plasma is added to thromboplastin

and calcium in oxalated blood

• Normal = 12 seconds

• Prolonged in

– Deficiency of I, II, V, VII & IX

– Liver disease

– High dose heparin

INR

• International normalized ratio is determined to standardize PT

• (PTtest /PTnormal)ISI

• ISI : 1-2

• INR– Normal = 0.9—1.3

– High = 4– 5 (bleeding)

– Low = 0.5 (clot)

– Warfarin therapy = 2– 3

DisorderBleeding

TimePlatelet count

PT APTTFibrinogen

Assay

Thromboc-ytopenia

Prolonged Decrease Normal Normal Normal

Vit – K Deficiency

Normal Normal Prolonged Prolonged Normal

Qualitative Platelets Defects

Prolonged Normal Normal Normal Normal

Classic Hemophilia

Normal Normal Normal Prolonged Normal

Christmas Disease

Normal Normal Normal Prolonged Normal

Von Willebrand

DiseaseProlonged Normal Normal Prolonged Normal

DIC Prolonged Decrease Prolonged Prolonged Prolonged