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).
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.
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
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
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.
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
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