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 activation degranulation(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 change 2) 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 births account for 90% of congenital bleeding disorders Hemophilia 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 tissue Sites: calf Symptoms: pain, swelling, muscle spasm Complications: nerve compression, contracture

Other Sites of Hemorrhage Abdomen GI tract Intracranial bleeds Around 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 A Fac viii preparations Cryo DDAVP Hemophillia B Fac ix CPP

General Avoid NSAIDs Avoid contact sports Avoid IM injections Good dental care Education – life long management Acute 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…..