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.
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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
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• 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
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Hemophilia A
Hemophilia B
Vitamin K deficiency
Von Willebrand Disease
Platelet and vessel wall defects usually present as
• skin and mucous membranesPetechie,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
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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
Severe
% normal
factor level
< 1%
Moderate
1 - 5%
Mild
6 - 20 %
Causes of bleeding
bleeding after trivial
injury or spontaneous
bleeding after minor
injury; occasional
spontaneous bleeds
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…..