Pathology of Bleeding Disorders:

Dr. Shashidhar Venkatesh MurthyA/Prof. & Head of Pathology

Learning Outcomes:

Discuss normal hemostasis, how bleeding stops.Discuss common bleeding disorders:

1. Common Blood Vessel disorders.

2. Common Platelet disorders.

3. Common Coagulation disorders.

4. Hypercoagulability/Thrombophilia disorders.

Discuss Pathology of each:• Clinical features, Pathogenesis & Laboratory diagnosis.

At the end of the session student will be able to,

Less More

Top Disorders:• Thrombocytopenia, ITP.• Vit-K deficiency.• Heparin, Warfarin, Aspirin• Cong: Haemophilia, VWD

Bleeding Disorders - Clinical

Normal Hemostasis Components:

1. BV – Vasoconstriction

2. Platelet plug formation

3. Activation of Coagulation – stable fibrin plug.

4. Activation of fibrinolysis – clot dissolution.

Injury

BV spasm

Plt. plug.

Coagulation

Fibrinolysis

Haemostasis overview:

BV Injury

PlateletAggregation

Blood Vessel Constriction

Coagulation Cascade

Stable Fibrin Plug

ReducedBlood flow

Plasma

Primary hemostatic plug

Blood Vessel

PlateletActivation

Fibrin formation*

Platelets

Injury

BV spasm

PLt. Act.

Coag.

FibrinolysisAnticoagulantsDisorders

ThrombophiliaDisorders Fibrinolysis

Disorders of Blood vessel Platelets Coagulation

LAB TEST:PT ~10 sec.Prothrombin Time. Factor 7

LAB TEST:aPTT ~20 sec.Activated Partial Thromboplastin Time.Factor 12, 9, 8

Bl. Clot

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This is the reason medical profession is considered special…!

Clinical bleeding symptoms: Petechiae <3mm

Purpura <1 cm

Echymosis >1cm

Hematoma

Blood Vessel / Platelet disorder

Trauma / Coagulation

Key Words:• Hemostasis• Primary plug• Sec. / stable plug• Blood clot.• Plt. Aggregation.• Plt. Adhesion• Plt. Activation• Coagulation• Thrombosis• Thrombolysis• Thrombophilia

Superficial / Deep Bleeding

A. Superficial & small Platelet & BV disorderB. Deep & Big Coagulation disorder

Platelet / BV Coagulation

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Bleeding Disorders: ClassificationPlatelet

AggregationBlood Vessel Constriction

Coagulation Cascade

Platelet Disorders:Function disorder

• Drugs – Aspirin• Kidney failure: uremia.

Thrombocytopenia:• Immune - ITP• Drugs, viral Infection• Aplastic anemia.• Chemotherapy.

Blood Vessel Disorders:Hereditary

• H.H.telangiectasia• Marfans sy.

Acquired• Simple easy bruising• Aging,Scurvy, • Drugs - steroids• Viral infections.

Coagulation Disorders:Hereditary:

• Haemophilia A, B• Von Willebrand’s

Acquired:• Liver disease.• Drugs - Heparin.• Inhibitors – immune.• Blood Transfusion

DIC – Disseminated Intravascular Coagulation All factor deficiency – Septicemia

“Thinking” should become your capital asset, no matter whatever ups and downs you come across in your life.” - Wings of Fire: An Autobiography of Dr. APJ Abdul Kalam.

Disorders of Haemostasis:

Blood vessel & Platelet disorders

Shashidhar Venkatesh Murthy B.Sc, MBBS, MD(path), GCTT, MBA(Edu), IFCAP(USA)

A/Prof. & Head of Pathology

Dengue – Hemorrhagic fever

Purpura in viral infections: Direct vascular damage, immune vasculitis leading to platelet activation & Coagulation.

BV & Plt

Spleen

Coag.

Bone Marrow Circulation

Thrombocytopenia: Commonest bleeding.Immune, Bone marrow dis, drugs, infections, Spleen

ITP: Immune Thrombocytopenic Purpura.

Autoimmune disorder. IgG Ab against plt. Mem. glycoproteins.

• Destroyed in Spleen. Thrombocytopenia, giant plts.• Insidius onset, Petechiae, purpura, easy bruising.

Acute & Chronic types.• Acute (children, post infections) • Chronic (females, 20-40y, Autoimmune)

Platelet counts & bone marrow examination.• BM: Increased Immature megakaryocytes.• Blood: Thrombocytopenia with giant platelets.• Other hemostasis tests normal.

Acute ITP: Petechiae

Chronic ITP: Female 28y.

Vit-K Deficiency: Green Veg & Intestinal bacteria. Deficiency of 2,7,9 & 10, C & S. Diet, Drugs & Liver Disease Warfarin * Lab: PT. Normal PTT (F7)

Warfarin

Factors: 2,7,9,10

Von Willebrand Disease:• Commonest Cong. Bl. Disorder.

• Autosomal recessive (M:F)

• Deficiency of vWF & F VIII*

• Both Plt & Coag. Disorder.• Type-1 85%, Quantitative, mild.

• Type 2 – Qualitative, rare.

• Type 3 – total absence, rare.

• Easy bruising & muco-cutaneous bleeding. Petechiae, Purpura.

• Lab Diagnosis:

• Prolonged bleeding time & normal coagulation time (mild F8 def.).

• Normal platelet count.

Plt & F VIII

Haemophilia-A X linked. Xq 2.8, Factor VIII def. Males affected, Female carrier. Factor level of >30% normal. Factor level <1%, 1-5%, >5% mild Wound bleeding & Hematoma. aPTT prolonged PT normal,

FVIII assay. Treat: FVIII. Haemophilia B: similar, F IX def.

Mild >5%

Mod 1-5%

Severe <1%

Chronic deformity

DIC: Disseminated Intravascular Coagulation.

Excess whole body activation of hemostasis Consumption of factors Bleeding.

Cause / Etiology: (infection, trauma, cancer)• Tissue factor release into circulation - trauma• Or Widespread endothelial damage - infection

Morphology / Clinical features:• Thrombosis, Severe bleeding, shock, renal failure.

Laboratory Diagnosis:• All tests abnormal*

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Anticoagulants & Hypercoagulability Disorders.

Heparin

WarfarinWarfarin

Bl. Clot

Thrombophilic disorders:

Hereditary:• Factor V Leiden (resistant to breakdown)• Protein C or S deficiency (anticoag.).• Prothrombin Gene mutation (hyperact.)

Acquired:• CVS disorders – MI, DM, HPTN.• Major trauma or inflammation or

malignancy – procoagulants.• Drugs - Oestrogen therapy.• Hyperhomocyteinaemia (rarely hereditary)• Antiphospholipid syndrome.

• Lupus anticoagulant & Anti cardiolipin Ab.

• Arterial thrombosis• Thromboembolism• Venous thrombosis• Abortions.

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- Martin Luther King Jr.

Students today enticed by modernity, have become oblivious to their

identity & purpose in life.

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grow into the likeness of that which is noble and lofty.

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Why only PT abnormal in Vit-K def?

Ans: Shortest half life…!

Why no effect?

Vit-K Liver Coag. Factors 2,7,9,10 – both PT & aPTT should raise…?