Blood disorders

What is hematology?

• Hematology is the study of blood and is concerned mainly with the formed elements in the blood.

• The formed elements in the blood include:– The white blood cells (leukocytes) which include the

neutrophils, eosinophils, basophils, monocytes, and lymphocytes (.

– The red blood cells (erythrocytes)– The platelets (thrombocytes)

• All of the formed elements in the blood are derived from same pluripotential stem cell in the bone marrow

What is hematology continued

• Erythrocytes function in the transport of oxygen to the tissues.

• Leukocytes function in both specific (immune responses) and non-specific defenses against foreign invasion.

• Thrombocytes function in hemostasis or blood clotting.

• Hemostasis • Disorders of bleeding • Anemia • Blood malignancies

Hemostasis

definition

• Maintenance of fluidity of blood while in vessel and formation of hemostatic plug on vascular injury

Balance between clot formation and bleeding is maintained

Hemostasis involves

• Clot formation • Anti clotting mechanisms

At a site of a vascular injury

1.Vasoconstriction

2.Primary hemostatic plug formation

3.Secondary hemostasis due to activation of coagulation cascade by tissue factor and phospholipid via extrinsic pathway- the end result being fibrin which traps the cells in the blood forming a clot

Vasoconstriction

• due to local neural response, and release of endothelin from the endothelium vessels constricted

Primary hemostatic plug formation

due to platelet adhesion activationdegranulation(ADP, TXA2) recruitment of other platelets

• In a site of vessel wall injury platelets in circulation comes in to contact with the ECM

• On contact with ECM constituents, platelets undergo 3 reactions:

1) ADHESION and shape change2) SECRETION (release reaction)3) AGGREGATION

• PLATELET ADHESION

• To sub-endothelial ECM constituents• Bridged by vWF, a product of endothelial cells

• PLATELET SECRETION

• Occurs soon after adhesion• Platelets release ADP and calcium• ADP activation of platelets is essential for

platelet aggregation, further release of ADP

Platelet aggregation

• product of platelet set up a reaction leading to build-up of an enlarging platelet aggregate, the primary hemostatic plug

• Vascular and platelet responses are important in reducing bleeding but their activity is limited.

• To arrest bleeding the proper ‘clot’ should be formed

• This is brought about by the clotting cascade

Coagulation cascade

• The coagulation cascade is essentially a series of enzymatic conversions, turning inactive proenzymes into activated enzymes and culminating in the formation of thrombin.

• Thrombin then converts the soluble plasma protein fibrinogen into the insoluble fibrous protein fibrin.

• This results in formation of the definitive clot

Anti clotting mechanism• Once activated the coagulation cascade must be restricted to the local

site of vascular injury to prevent clotting of the entire vascular tree.• Regulated by natural anticoagulants

• Anti thrombin III• Protein C and Protein S• Tissue palsminogen

• With onset of coagulation cascade, fibrinolytic cascade is also activated to limit the the size of final clot

• Primarily accomplished by plasmin

Disorders of hemostasis

• Clot formation inappropriately -thrombosis

• Bleeding disorders

Bleeding disorders

Types of skin bleeds –terminology

• Petechie - Minute (1- to 2-mm) hemorrhages into skin, mucous membranes, or serosal surfaces

Types of skin bleeds –terminology

• Purpuras - Slightly larger i.e 3- to 5-mm hemorrhages are called purpuras

Types of skin bleeds –terminology

• Ecchymoses - Larger i.e 1- to 2-cm or more subcutaneous hematomas (bruises)

Bleeding disorders

• Vessel wall disorders • Platelet disorders • Coagulation disorders

Vessel wall disorders

• Defective collagen due to connective tissue disorders, vitamin C deficiency

Platelet disorders

• Low platelet count (thrombocytopenia )• Platelet function disorders

Causes of thrombocytopenia • Decreased platelet production-bone marrow disorders like cancers,aplastic

anemia,-drugs, infections • Increased destruction-immune thrombocytopenic purpura-DIC-HUS• Enlarged spleen

Coagulation disorders

• Hemophilia A• Hemophilia B• Vitamin K deficiency• Von Willebrand Disease

Platelet and vessel wall defects usually present as• skin and mucous membranes-

Petechie,Ecchymosis• Gum bleeding and epistaxis• Menorrhagia• Gastrointestinal bleeding• Intracranial bleeding

Clotting factor disorders may present as

• Bleeding Into joints - Haemarthroses• Into deep tissues – Hematoma• Muscle bleeds

Coagulation disorders

• Hemophilia A• Hemophilia B• Vitamin K deficiency• Von Willebrand Disease

Question

• why does vitamin K deficiency give rise to bleeding?

Hemophilia A & B

clinically similar:occur in approximately 1 in 5,000 male birthsaccount for 90% of congenital bleeding

disordersHemophilia A is approximately 5 times more

common than B

Etiology

Inherited as a sex linked recessive trait with bleeding manifestations only in males

genes which control factor VIII and IX production are located on the x chromosome; if the gene is defective synthesis of these proteins is defective

female carriers transmit the abnormal gene A disease of males

Classification

% normal factor level

Causes of bleeding

Severe < 1% bleeding after trivial injury or spontaneous

Moderate

1 - 5% bleeding after minor injury; occasional spontaneous bleeds

Mild 6 - 20 % following major trauma, surgical or dental procedures

Diagnosis

• Atypical bleeding at circumcision or bruising at neonatal vaccines

• Toddlers with lip bleeding or unusual bruising when learning to walk

• Hx of affected males on mother’s side• Elevated PTT• Factor assays

Clinical Features – Joint Bleeds

Joints (Hemarthrosis) Knees, ankles and elbows most common sites begin as the child begins to crawl and walk

Single joint bleed: stiffness, swelling, pain With repeated bleeding into same jt---arthropathy->

stiffness and contractures

Clinical Features – Muscle Bleeds

Bleeding into muscle or soft tissueSites: calfSymptoms: pain, swelling, muscle spasmComplications: nerve compression,

contracture

Other Sites of Hemorrhage

AbdomenGI tractIntracranial bleedsAround vital structures in the neck

Can cause death…

• They have high risk of HIV,Hep B and Hep C due to repeated transfusion of blood products

Management

Specific Hemophillia AFac viii preparations CryoDDAVP

Hemophillia BFac ix CPP

General

Avoid NSAIDsAvoid contact sports Avoid IM injections Good dental careEducation – life long managementAcute and long term management of

musculoskeletal problems

Von Willabrand disease

Read…..

Investigations in bleeding disorders

• Bleeding time-vessel wall and paltelet defects detected

• Prothrombin time (PT)-prolonged in disorders of the extrinsic pathway

• Activated partial thromboplastin time(APTT) –prolonged in intrinsic pathway disorders

Thank you…..