Thrombotic disorders

virchow´S TriadAlterations in blood flow (ie,stasis)Vascular endothelial injuryAlterations in the constituents of the blood(ie,

inherited or acquired hypercoagulable state )

Classification of thrombophilias Inherited protein C and S Antithrombin III FVL mutation 12-19% Methyltetrahydrofolate reductase mutation (MTHFR) Prothrombin G20210A mutation.6-8% ( PGM) Antiprotein Z deficiency. Dysfibrinogenemia .

Acquired lupus anticoagulant Anticardiolipin antibodies Activated protein C resistance Hyperhomocystinemia

Acquired disorders Malignancy Presence of a central venous catheter Surgery , especially orthopedic TraumaPregnancyOral contraceptivesHRTTamoxifen, thalidomide, Lenalidomide ImmobilizationCongestive failurePolycytemia vera, thrombocythemiaParoxysmal nocturnal hemoglobinuria Inflammatory bowel disease Nephrotic syndrome

Anatomic risk factors for DVTPaget-Schroetter syndrome .

May-Thurner syndrome (iliac vein compression ).

Inferior vena cava abnormalities (Agenesis, Hypoplasia, or Malformation )

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Elevated clotting factorsVIII:C>150 percentXI:A>121 percentIX:A>129 percentTAFI>122 percent(thrombin activatable

fibrinolysis inhibitorInterleukin 8>8.2 pg/ml

Thrombotic disordersLaboratory tests for the diagnosis

Family history of thrombosisFamily history of thrombophilias

Prior unexplained fetal deathPrior sever early onset preeclampsia (<34 weeks)

Prior sever IUGR Prior sever placental insufficiency

abnormal Doppler velocimetry abnormal placental histology

oligohydramnious

APOadverse pregnancy outcomeMaternal venous thromboembolism arterial thrombosis sever preeclampsiaPlacental thrombosis and infarcts abruptioFetal recurrent miscarriage sever IUGR Fetal demise Stroke

Factor V Leiden FV Leiden is a mutation gene which leads to phenotype of

APCR(activated protein C resistance). Prothrombin G21210A is mutation in factor II gene.Antithrombin III(AT): heparin cofactor.{ type I and type II defects.AT antigen measurement by ELISA is normal in type II AT

deficiency.as many as 28% .and will be missed.Protein C .Protein S .Dysfibrinogenemia. may cause bleeding or thrombosis .diagnosis

can be confirmed by study of fibrinogen antigen.Factor VIII activity elevation .Factor IX and XI elevations .Antiphopholipid antibodies (LA ,ACA ,ß2-glycoprotein I) .Hyperhomocysteinemia .

Variables affecting testsPregnancy .Oc pills .HRT.Thrombotic event .Systemic illness.Heparin or warfarin

APS clinical feature Thrombosis ,PE ,TIA ,Thrombocytopenia.Migraine headache Transverse myelitisChorea Syndromes resembling multiple sclerosis

Management of thrombosis in APS

Heparin should be continued for at least 5 days, and should be overlap with warfarin

Thrombophilias ,perinatal stoke. And cerebral palsy

Perinatal arterial ischemic stroke (PAS).Occurring between 28 weeks and 28 days of

post natal life,Usually occurs before about 72 hours of

postnatal lifeFocal arterial infarction of brain and cerebral

venous thromboses .unilateral or bilateral PAS.MRI or CT Scan.Ultrasonography is not a sensitive detector of

stoke.

Clinical feature of PASHypotoniaApneas Neonatal seizures intractable to medical

therapy.Asymmetry of movementThe diagnosis is 4 to 8 months.Delayed language developmentMajority of children who had cerebral palsy

caused by perinatal stroke were not recognized to be affected in the newborn period.

Pregnancy related stroke in the mother Risk factors :

infection ,migraine ,thrombophilias ,APS ,SLE ,heart disease ,pre-eclampsia ,diabetes ,smoking ,obesity ,older age ,prolonged bed rest .C/S .

In the fetus .high hematocrit ,injury to neck vessels .newborn dehydration ,hypotension ,infection ,intravascular catheters ,

Combination of clinical outcomes that should prompt a consideration of underlying thrombophilias

Abruption Retroplacental hematom Recent villous infarction Intruterine growth restriction preeclampsia

The use of unfractionated heparin and low molecular weight heparin in pregnancyWarfarin is generally avoided during pregnancy and is

safe to use postpartum .UH mean molecular weight 15000 daPTT >1.5 to 2.5mean control . thromboprophylaxis with UH in first trimester 5000iu

BID ,second trimester 7500iu BID ,in third trimester 10000iu BID

Acute Therapeutic dose of UH in pregnancy: initial bolus 80 units/kg, and continuous infusion 16 to 18 units/kg/h for 5 day, then converted to intermittent subcutaneous heparin

Patients with mechanical cardiac valves should receive therapeutic anticoagulation during pregnancy .

LMWHMean molecular weight 500 d ,do not cross the

placenta in any trimester.Anti Xa activity must be measured.Are excreted renally.Twice daily dosing may be required .Osteoporosis and thrombocytopenia may be lessTherapeutic range for anti Xa level is 0.5 to

1.0IU/mL Monitoring levels every 2 to 4 weeks .

Intrapartum management6 hours after vaginal delivery and 12 hours after C/S

prophylaxis is resumed.12 to 24 hours before discontinuing LMWH for

regional anesthesia .Some clinicians switch patients on LMWH to UH

10000units every 12 hours at approximately 36 weeks gestation.

For high risk patients on therapeutic intravenous UH therapy stopped 3 to 6 hours before delivery .

After delivery full anticoagulant with coumadin started concomitantly .

Initial dose of coumadin should not exceed 5 mg .Postpartum anticoagulant continue for 6 to 8 weeks

and for recent VTE treatment with coumadin continued for 3 to 6 months.

Prosthetic cardiac valves in pregnancyACOG and ACC recommendation :

enoxaparin sodium patients should be started on 1 mg/kg every

12 hours and to achieve peak anti-Xa levels 1.0-1.5 IU/mL

The addition of aspirin 82mg/d. was also felt to be prudent.

Time of delivery Fetal assessment with NST beginning at >36

weeks of gestation and delivery at 39 weeks of gestation in the abernce of preeclampsia ,abruption ,IUGR .

If obstetrical complications are present ,fetal surveillance should be earlier .

inherited dysfibrinogenemiaSilent 55%Hemorrhagic 25%Thrombotic diathesis 10-20%Thrombotic and bleeding 2%A rare cause of thrombophilias 0.8%The prevalence of thrombosis

(venous/arterial)among patients with dysfibrinogenemia is

around 10 to 20% .

Acquired disorders Liver disease Renal carcinomaIsotretinoin therapyBiliary obstructionAcute DIC Cryofibrinogenemia is seen in autoimmune

disorders ,malgnancy ,thrombotic disorders ,and infections (hepatitis C ) and DIC .symptoms include sensitivity to cold ,Raynauds phenomen ,purpura ,urticaria ,skin ulcerations or gangrene , and thrombosis .

Diagnosis and treatmentPTTTaPTT

Fibrinogen replacement prior to surgery >100 mg/DLPregnancy: weekly measurement and requirement

from 2 g twice weekly during the first trimester to 5 g three to four times per week at term.

During labor: fibrinogen level 150 to 200 mg/dl.After 24 hours. fibrinogen level >50 mg/dl should be

maintained .

Available treatment modalitiesCryoprecipitate and FFP :one unit (10 to 15 ml) contains

approximately 200 to 400 mg fibrinogen .each unit raises fibrinogen 7 to 10 mg/dl with half life of two to four days .

1-2 unit of cryo per 10 kg body weight.Maintenance dose of approximately one third of the

initial dose is infused daily for two to three weeks following major surgery.

Complications : allergic reactions, transmission of infection ,and thrombosis ,

Fibrinogen concentrate: Dose(mg)=target fibrinogen(mg/dl)-measured fibrinogen

level +1.7 xbody weight(kg)