The document discusses various thrombotic disorders including: 1. Congenital and acquired thrombotic disorders are characterized by the formation of blood clots that obstruct blood flow. 2. Some inherited prothrombotic mutations that can cause thrombosis include Factor V Leiden, prothrombin 20210A, and deficiencies of antithrombin, protein C, and protein S. 3. Acquired conditions like malignancy, immobilization, surgery, pregnancy, estrogen use, and heparin-induced thrombocytopenia can also trigger blood clots when combined with inherited mutations.

1. Thrombotic Diseases
Somu.Venkatesh
Roll 118

2. Thrombotic disorders
Congenital and acquired
diseases characterized
by formation of thrombus
that obstructs vascular
blood flow locally or
detaches and embolizes
to occlude blood flow
downstream
(thromboembolism).

4. Classification:
1. Familial – physiological
2. Non-familial (acquired) – physiological or
pathological

5. Acquired
Prothrombotic
Stimulus
One or more
Inherited
Prothrombotic
Mutation(s)
Thrombosis
Acquired
Prothrombotic
Stimulus
One or more
Inherited
Prothrombotic
Mutation(s)
Thrombosis
Factor V Leiden
Prothrombin 20210A
Protein C deficiency
Protein S deficiency
Antithrombin deficiency
Hyperhomocysteinemia
Antiphospholipid antibodies
Malignancy
Immobilization
Surgery
Pregnancy
Estrogen
Heparin-induced thrombocytopenia

6. Antithrombin deficiency
 It is familial deficiency of AT
 Autosomal dominant
 70% of affected individuals will have an
episode of VTE before age of 60 years.
 Pregnancy is a high-risk period for VTE
and this requires large doses of
LMWH(≥100U/kg/day).
 AT concentrate (either plasma derived or
recombinant) is required for
cardiopulmonary bypass and may be
used as an adjunct to heparin in surgical
prophylaxis.

7. Antithrombin deficiency
 Increased thrombosis- DVT/PE,
mesenteric vein
 Diagnosis- low functional level of AT-III
 Treatment- large dose
heparinlifelong Warfarin

8. Protein C and S deficiencies
 Protein C and S are Vit K-dependent
natural anticoagulants involved in
switching off coagulation factor activation
(factor Va and VIIIa) and thrombin
generation.
 Inherited deficiency of either protein C
and protein S results in a prothrombotic
state with a fivefold relative risk of VTE
compared with the background
population.
 Treatment- heparin, followed by Warfarin

9. Factor V Leiden
 Results from single base pair mutation
which prevents cleavage and hence
inactivation of activated factor V.
 Heterozygous: 5-10 times increased
risk for TE.
 Homozygous: 50-100 times.

10. Factor Va
Arg 306 Arg 506 Arg 1765
Arginine
CGA
Glutamine
CAA
Factor Va resistant to APC cleavage
Factor V Leiden

11. Relative Risk for
Venous Thrombosis
Factor V Leiden Heterozygote x 7
Factor V Leiden Homozygote x 80
Oral Contraceptives x 3
Oral Contraceptives + Factor V Leiden x 35
Leiden Study Group Data

12. Prothrombin G20210A
 Due to mutation in the non-coding 3´
end of the prothrombin gene is
associated with an increased plasma
level of prothrombin. Increased levels
of prothrombin enhanced thrombin
formation.
 In the heterozygous state, it is
associated with a 2-3 fold increase in
risk of VTE
 Only way for diagnosis: DNA-PCR
technique.

13. Antiphospholipid
Syndrome(APS)
 Syndrome characterized by venous
and/or arterial thrombosis,
thrombocytopenia, or recurrent fetal
loss; associated with antibodies to
phospho-lipid-protein Complexes.
 May present in isolation (primary APS)
or in associated conditions like

14. Conditions associated with
secondary APS
 Systemic lupus erythematosus
 Rheumatoid arthritis
 Systemic sclerosis
 Behcet’s syndrome
 Temporal arteritis
 Sjögren’s syndrome

15. Antiphospholipid Syndrome
 Antiphospholipid antibodies are
heterogenous and typically are directed
against proteins which bind to
phospholipids.
Targets for antiphospholipid antibodies
 ß2-glycoprotein 1
 Protein C
 Annexin V
 Prothrombin (may result in haemorrhagic
presentation)

16. Clinical features
 Adverse pregnancy ourcome
Recurrent 1st trimester abortion (≥3)
Unexplained death of morphologically
normal fetus after 10 wks of gestation
Severe early pre-eclampsia
 Venous thromboembolism
 Arterial thromboembolism
 Livedo reticularis, catastrophic APS,
transverse myelitis, skin necrosis,
chorea

17. Investigation
 Anticardiolipin antibody test
 Lupus anticoagulant test

18. Management
 Arterial thrombosis, typically stroke,
associated with APS should be treated
with warfarin, as opposed to aspirin.
 APS-associated VTE is one of the
situation in which the predicted
recurrence rate is high enough to
indicate long-term anticoagulation after a
first event.
 In women with APS, it is likely that
intervention with heparin and possibly
aspirin increases the chance of
successful pregnancy outcome.

19. Disseminated Intravascular
Coagulation

20. Disseminated Intravascular Coagulation
It is an acquired condition in which normal physiology of
coagulation is disturbed leading to widespread intravascular
coagulation process associated with injury to
microvasculature which results in organ dysfunction,
capillary leak & shock.
Occurs due to simultaneous action of the following 4
mechanisms
Increased thrombin generation
Suppressed physiological anticoagulant pathways
Activation & subsequent impairment of fibrinolysis
Activation of inflammatory pathways

21. ETIOLOGY
• Infection/sepsis
• Trauma
• Obstetric, e.g. amniotic fluid embolism, placental abruption, pre-
eclampsia
• Severe liver failure
• Malignancy, e.g. solid tumours and leukaemias
• Tissue destruction, e.g. pancreatitis, burns
• Vascular abnormalities, e.g. vascular aneurysms, liver
haemangiomas
• Toxic/immunological, e.g. ABO incompatibility, snake bite,
recreational drugs

22. Disseminated Intravascular Coagulation
Bleeding signs and symptoms
Petechiae
Purpura
Arterial line oozing
Venipuncture site
bleeding
Clinical manifestation

23. ISTH Scoring

24. treatment
Disseminated Intravascular Coagulation
Elimination of the precipitating factor if
possible
Replacement of coagulation factors and
platelets
Inhibition of the clotting process with
heparin or other agents.

25. Thrombotic Thrombocytopenic Purpura
 Rare
 Enzyme ADAMTS13, responsible for cleaving
large multimers of vWF into normal functional
units and its deficiency due to antibodies
binding to it and results in large vWF
multimers which cross-link platelets.
 Causes extensive microscopic thrombosis,
with platelet consumption
 Microthromboses cause end- organ
dysfunction
 Hemolysis is due to shear stress,
producing schistocytes

26. Cause
 Idiopathic- autoimmune,
severely decreased ADAMTS13 activity
 Secondary- associated with
 Cancer
 BMT
 Pregnancy
 HIV-1 infection
 Drugs- Quinine, Clopidogrel, cyclosporine, Tacrolimus,
Mitomycin-C, Interferon
 Hereditary- Upshaw-Schulman syndrome

27. Clinical presentation-
 pentad
 Thrombocytopenia
 Microangiopathic haemolytic anaemia
 Neurological sequelae
 Fever
 Renal impairement

28. Management
 Diagnosis
 clinical,
 thrombocytopenia,
 normal PT/aPTT
 Treatment
 Plasmapheresis, with supportive treatment
 Refractory- steroids, aspirin, cyclophosphamide,
rituximab
 Splenectomy

29. Thank you