BLEEDING DISORDERS

Definition
Petechiae
Purpura
Ecchymosis
Telengiectasia
Hematoma
Hemarthrosis
Petechiae – tiny pinpoint areas of
hemorrhage
Purpura- area of h.age more
than3mm
Ecchymosis – extravasated blood in
skin more than 1cm of diameter
Telangiectasia– spots resulting from
localised dilated blood vessels,
blanch on pressure
What is primary hematosis?
What is secondary hematosis?
What are vessel wall abnormalities?
Drugs producing thrombocytopenia
Spontaneous bleeding occurs when
platelet count is-
Petechiae and purpura occurs in
Deep tissue bleeding occurs in
HIT
Clinical features of ITP
Pentad of TTP
Bernard soulier syndrome
Hemostasis
Vascular disorders
Hereditary – hereditary hemorrhagic
telengiectasia(weber osler rendu
syndrome)
Immune disorder- HSP-purpura, abd
colic, polyarthralgia, acute GN-immune
complex circulation in blood vessels
Collagen defect- scurvy, ehlers
syndrome, cushing syndrome
Perivascular amyloidosis- AL chain
Infections – septicemia,
meningococcemia, rickettosis
Drugs
Platelet disorders
Decrease in count-
Thrombocytopenia
Defective platelet function
1. bernard soulier syndrome
2. glanzman thrombosthenia
3. storage pool disorder
Thrombocytopenia
Count less than 1,50,000 /μl
20,000-50,000 – post traumatic
bleeding
Less than 20,000 – spontaneous
bleeding
Spontaneous bleeding occurs in
skin and mucous membrane of
GIT and genitourinary tracts and
intracranial bleed
Thrombocytopenia
Decreased production
Increased destruction
Sequestration
Dilutions
Decreased production-platelets
Bone marrow failure- aplastic anemia
Bone marrow replacement- acute
leukemia, disseminated cancer,
granulomatous disease
Ineffective hematopoiesis – MDS
Nutritional def – B12&folate
deficiency
Drug induced – alcohol, thiazides,
cytotoxic drugs
Infections – measles, HIV
Increased destruction
Immunologic destruction
Primary autoimmune- chronic ITP,
acute ITP
Secondary autoimmune- SLE,
lymphoma, post transfusion, drugs,
infections
Non immunologic destruction
DIC, thrombotic microangiopathies,
giant hemangiomas
Sequestration – hypersplenism
Dilution - transfusions
Acute ITP
Autoantibodies to platelets
Children
Symptoms appear suddenly, 1-2
weeks after viral illness
Self limited, resolving within 6 months
Persistent thrombocytopenia in 20%
Glucocorticoid -treatment
Chronic ITP
Autoantibody mediated destruction of
platelets
Primary and secondary
Primary – idiopathic
Secondary – SLE,HIV, B cell
lymphoma as CLL
Pathogenesis
Autoantibodies against platelet
membrane glycoproteins – IIb-IIIa, Ib-
IX ; IgG class
Anti-platelet antibodies acts as
opsonins- recognised by IgGFc
receptors expressed on phagocytes
Opsonised platelets are destroyed in
spleen
Morphology
Thrombocytopenic purpura – spleen, BM
and secondary changes due to bleeding into
tissues
Spleen – normal size, congestion of
sinusoids, enlargement of splenic follicles,
prominent reactive germinal centres
Megakaryocytes in the splenic sinusoids –
extramedullary hematopoiesis
Bone marrow – increased
megakaryocytes
Few megs- immature, large, non
lobulated, single nuclei
Peripheral smear – large platelets
Clinical features
Adult women less than 40 yrs;
3:1, females are more affected
Sudden onset, bleeding into skin and
mucosa
Cutaneous bleeding- petechiae in
dependent portion , ecchymoses
Easy bruishing, nose bleeds, gum
bleeding, & hemmorhages into soft
tissues
Melena, hematuria, excessive
menstrual flow
Subarachnoid hemorrhage and
intracranial hemorrhage – fatal
Spleenomegaly and
lymphadenopathy in secondary ITP-
lymphoid lesions
Lab findings
Thrombocytopenia
PS- large platelets
BM- N or increased megs
PT and APTT – normal
Diagnosis of exclusion
Glucocorticoids
Spleenectomy
Immunoglobulins
ITP
Heparin induced
thrombocytopenia [ HIT]
Type I and typeII thrombocytopenia
Type I – immediately after starting
heparin
Resolve spontaneously and is mild
Type II – serious
5-14 days after therapy
Leads to life threatening venous and
arterial thrombosis
Due to antibody bind to heparin-platelet
complexes
Thrombosis inspite of
thrombocytopenia
Heparin should be stopped
immediately
Low molecular weight heparin
reduces the risk
Thrombotic microangiopathies
TTP- deficiency of ADAMTS13( v WF
metalloprpteinase)
May be inherited or acquired
HUS
Both are caused by excess activation
of platelets – deposit as thrombi in
small vessels
Microangiopathic hemolytic anemia
and widespread organ dysfunction
TTP
ADAMTS13 degrades vWF
In the absence of this enzyme, vwf
multimer accumulates and activate
platelet aggregation and adhesion –
thrombus formation
Deficiency – inherited or acquired
TTP

Department of pathology
HUS
Associated with infectious
gastroenteritis by E.coli- shiga like
toxin
Toxin alters endothelial cell function –
platelet activation and aggregation
Children and older adults
Bloody diarrhea
Rarely progress to renal damage and
death
Atypical HUS
Defects in complement factorH,
membrane cofactor protein or factor I,
three proteins that prevent excessive
activation of alternative complement
pathway
Inherited or acquired autoantibodies
Therapeutic antibodies and
immunosuppression
Dialysis and renal transplant
Defective platelet function
Inherited or acquired
3 types
1. defects of adhesion
2. defects of aggregation
3. disorders of platelet secretion
Structure of platelet
Bernard –soulier syndrome –
defective platelet adhesion to sub
endothelial matrix
Inherited deficiencies of platelet
membrane glycoprotein complex Ib-
IX
Is a receptor for vwf – essential for
adhesion
Severe bleeding manifestation
Glanzmann thrombasthenia –
defective platelet aggregation
Fail to aggregate in response to ADP,
collagen, adrenaline or thrombin
Deficiency or dysfunction of
glycoprotein IIb- IIIa ( helps in
binding)
Severe bleeding
Disorders of platelet secretion
Defective release of certain mediators
of platelet activation , as
thromboxanes,& granule bound ADP
Acquired defects of platelet
function
Aspirin and other NSAID induced
Irreversible inhibitor of enz
cycloxygenase
Inhibt synthesis of TxA2 & PGs- play
role in platelet aggregation and
release reactions
Uremia –defect in adhesion,
aggregation, and secretion
Tests for bleeding disorder
Platelet count
PS examination
Bleeding time- Duke’s, Ivy, and
template(2-7 mts)
Platelet functional analyser
Platelet adhesion studies
Platelet aggregation studies-
aggregometer
Flow cytometric detection of glycoproteins
on platelet surface
What is primary hematosis?
What is secondary hematosis?
Drugs producing thrombocytopenia
Spontaneous bleeding occurs when
platelet count is-
Petechiae and purpura occurs in
Deep tissue bleeding occurs in
HIT
Clinical features of ITP
Pentad of TTP
Bernard soulier syndrome
35yr /f, c/o menorrhagia for past 6
months, purpuric rash developed 6
days back. PT and APTT normal. BT
prolonged.
PS- large platelets, thrombocytopenia
BM- increased megakaryocytes with
nonlobulated nuclei.