HOW TO APPROACH TO A PATIENT WITH BLEEDING DISORDERS

EVALUATION OF THE BLEEDING PATIENT

DEFINITION

• Hemostasis

The arrest of bleeding from an injured blood vessel, involving the combined regulatory activity of vascular, platelet, and plasma factors

Primary Hemostasis

Vessel wall function Platelet functions of Adhesion, Aggregation

Secondary hemostasis

Plasma coagulation factors leading to fibrin deposition ,clot formation

Tertiary hemostasis

Clot retraction Cross link of fibrin clot Fibrinolysis

• Clotting The Coagulation of blood is a complex process by which fluid

form of blood changes to semi solid or solid form.• Bleeding

Extavasation of blood from an ruptured blood vessel to the internal or external tissue.

HEMOSTASIS AND THROMBOSIS

• Dependent on 3 factors:

Vascular endothelium Platelets Coagulation system

1. CLINICAL ASPECTS OF BLEEDING

1. CLINICAL ASPECTS OF BLEEDING

Evaluation of patients with bleeding is a multi-step process:

• Complete history

• Detailed physical exam

• Laboratory evaluation

HISTORY

Is there a personal or family history of bleeding after surgical procedures, dental procedures, childbirth, or trauma?

When the bleeding episode started?

Has the patient received medications that can cause or make worse a bleeding problem?

Many drugs can contribute to bleeding; semisynthetic penicillins cephalosporins

calcium channel blocker dipyridamolethiazides alcohol

quinine, quinidine chlorpromazine, sulfonamides INH, rifampin methyldopa phenytoin, barbiturates, warfarin, heparin, thrombolytic agents NSAIDs, ASA allopurinol

TMP/SMX

PHYSICAL EXAM

1. Assess volume status (correct shock if present)

2. Look for hepatosplenomegaly

3. Do a rectal exam for evidence of GI bleeding

4. Examine oropharynx for evidence of petechiae

HEREDIATARY TELANGECTASIAS

• Mouth: Gum Bleed Gum Hypertrophy Telangectasias Angular stomatitis

SUBCONJUNCTIVAL HAEMORRHAGE

PHYSICAL EXAM

Look for physical signs and symptoms of diseases related to capillary fragility:

Cushing’s syndrome, Marfan syndrome or exogenous steroids

"senile purpura” Petechiae secondary to coughing, sneezing, Valsalva

maneuver, blood pressure measurement

vasculitis ("palpable purpura")

Telangiectasias (Osler-Weber-Rendu syndrome) (HHT)PETECHIAE

VASCULITIS (PALPABLE RASH)

2. HEMATOLOGIC DISORDERS CAUSING BLEEDING

– Platelet disorders

– Coagulation factor disorders

CLINICAL DIFFERENTIATION

PLATELET DEFECTVS

COAGULATION DEFECT

PLATELETS DEFECTS

• Generally have immediate onset of bleeding after trauma

• Bleeding is predominantly in skin, mucous membranes, nose, GI tract, and urinary tract

• Bleeding may be observed as petechiae (<3 mm) or ecchymoses (>3 mm

COMPARISON OF PLATELET AND COAGULAYION DISORDERS

  Platelet Disorders Coagulation Factor Disorder

Site of bleeding Skin, mucous membrane and soft tissue

Deep in soft tissues (joints and muscles)

Physical Finding Petechiae, ecchymoses Hematoma, Hemarthrosis

Family History Autosomal dominant Autosomal or X-linked recessive

Bleeding after cuts and scratches

Yes No

Bleeding after surgery and trauma

Immediate, usually mild

Delayed (1-2 days), often severe

CLINICAL ASPECTS OF BLEEDING

COAGULATION DEFECTS

• "Deep" bleeding (in the joint spaces, muscles, and retroperitoneal spaces) is common. Observed on exam as hematomas and hemarthroses.

Hematoma

LABORATORY EVALUATION OF BLEEDING

LABORATORY EVALUATION OF BLEEDING

Platelet function von Willebrand factor vWDBleeding time In vivo test (non-specific)Platelet function analyzer (PFA) Qualitative platelet

disorders

BLEEDING TIME

• 5-10% of patients hospitalized patients have a prolonged bleeding time

• Most of the prolonged bleeding times are due to aspirin or drug ingestion

CBC and smear Platelet count ThrombocytopeniaRBC and platelet morphology TTP, DIC, etc.

Coagulation PT extrinsic/common pathways

PTT Intrinsic/common pathways

Coag. factor assays Specific factor deficiencies

50:50 mix Inhibitors (e.g., antibodies)

Fibrinogen assay Decreased fibrinogen

Thrombin time Qualitative/quantitative fibrinogen defects

D-dimer Fibrinolysis (DIC)

• Prolonged bleeding time does not predict excess surgical blood loss

• Not recommended for routine testing in preoperative patients

THROMBIN TIME

• Measures rate of fibrinogen conversion to fibrin

• Procedure:– Add thrombin with patient plasma– Measure time to clot

• Variables:– Source and quantity of thrombin

CAUSES OF PROLONGED THROMBIN TIME

• Heparin• Hypofibrinogenemia• Dysfibrinogenemia• Paraprotein• Thrombin inhibitors (Hirudin)• Thrombin antibodies

PLATELETS

APPROACH TO THE THROMBOCYTOPENIC PATIENT• History

– Is the patient bleeding?

2. Are there symptoms of a secondary illness? (neoplasm, infection, autoimmune disease)

3. Is there a history of medications, alcohol use, or recent transfusion?

• History4. Are there risk factors for viral infection?

5.Is there a family history of thrombocytopenia?

6. Do the sites of bleeding suggest a platelet defect?

• Assess the number and function of platelets

– CBC with peripheral smear– Bleeding time – Platelet aggregation study– PFA

CLASSIFICATION OF PLATELET DISORDER

• Quantitative disorders

– Abnormal distribution

– Dilution effect

– Decreased production

– Increased destruction

CLASSIFICATION OF PLATELET DISORDERS• Qualitative disorders

– Inherited disorders (rare)

– Acquired disorders• Immune• Medications• Chronic renal failure• Cardiopulmonary bypass• Liver disease

INHERITED PLATELET DISORDERS

• May-Hegglin : ThrombocytopeniaLarge plateletsNeutrophils – Dohle bodies

.Glazmann’s thrombasthenia: Congenital deficiency or abnormality of GP IIb-IIIa

• Bernard-Solier syndrome: Congenital deficiency or abnormality of GP Ib

ACQUIRED PLATELET DISORDERS• Decreased production: Ineffective thrombopoiesis - MDS

• Increased destruction:ImmuneNon-immune

• Poor aggregationINCREASED PLATELETS DESTRUCTION

ITP IS A DIAGNOSIS OF EXCLUSION !

COAGULATION FACTOR DEFECTS

Inherited Coagulation factor bleeding disorders

– vonWillebrand’s disease

– Hemophilia (A and B)

HEMOPHILIA

Clinical manifestations (hemophilia A & B are indistinguishable)

– Prolonged bleeding after surgery or dental extractions

– Hemarthrosis (most common)

– Soft tissue hematomas

– Other sites of bleedingUrinary tract

CNS, neck (may be life-threatening)

ACQUIRED BLEEDING DISORDERS:

– Vitamin K deficiency– Liver disease – Warfarin overdose– DIC– Inhibitors to CF

VITAMIN K DEFICIENCY

• Source of vitamin K :Green vegetables Synthesized by intestinal flora

• Required for synthesisFactors II, VII, IX ,XProtein C and S

• Causes of deficiency :MalnutritionBilliary obstructionMalabsorptionAntibiotic therapy

DIC

DISSEMINATED INTRAVASCULAR COAGULATION• Sepsis

• Trauma– Head injury– Fat embolism

• Malignancy

PATHOGENESIS OF DICConsumption ofcoagulation factors;presence of FDPs aPTT PT TT Fibrinogen

Presence of plasmin D-dimer

Intravascular clot PlateletsSchistocytes

HEMOSTASIS IN LIVER DISEASE

LIVER DISEASE AND HEMOSTASIS• Decreased synthesis of II, VII, IX, X, XI, and fibrinogen

• Dietary Vitamin K deficiency (Inadequate intake or malabsortion)

• Dysfibrinogenemia

• Enhanced fibrinolysis (Decreased alpha-2-antiplasmin)

• DIC

• Thrombocytopenia due to hypersplenism

MANAGEMENT OF HEMOSTATIC DEFECTS IN LIVER DISEASE

Treatment for prolonged PT/PTT

Vitamin K 10 mg SQ x 3 days - usually ineffective

Fresh-frozen plasma infusion: 25-30% of plasma volume (1200-1500 ml) (immediate but temporary effect)

Treatment for low fibrinogen

Cryoprecipitate (1 unit/10kg body

APPROACH TO BLEEDING DISORDERSSUMMARY

• Identify and correct any specific defect of hemostasis– Laboratory testing is always needed to establish the cause of bleeding

– Screening tests (PT,PTT, platelet count) will often allow placement into one of the broad categories

– Specialized testing is usually necessary to establish a specific diagnosis

• Use non-transfusional drugs whenever possible

• RBC transfusions for surgical procedures or large blood loss

THANK YOU!