Hypercoagulable States. Acquired versus inherited Acquired versus inherited “Provoked” vs...
-
Upload
abel-hancock -
Category
Documents
-
view
222 -
download
0
Transcript of Hypercoagulable States. Acquired versus inherited Acquired versus inherited “Provoked” vs...
Hypercoagulable Hypercoagulable StatesStates
Hypercoagulable Hypercoagulable StatesStates Acquired versus inheritedAcquired versus inherited ““Provoked” vs idiopathic VTEProvoked” vs idiopathic VTE Who should be tested for inherited Who should be tested for inherited
thrombophilia?thrombophilia? What tests should be done & when?What tests should be done & when? Anticoagulation recommendationsAnticoagulation recommendations Should family members be tested?Should family members be tested?
Virchow’s triadVirchow’s triad
Was VTE “provoked”?Was VTE “provoked”?
Medical and surgical historyMedical and surgical history MedicationsMedications Travel – air & groundTravel – air & ground Review of systems Review of systems Cancer screening historyCancer screening history
Was VTE “provoked”?Was VTE “provoked”?
Physical exam – including breast Physical exam – including breast exam, rectal exam, pelvic exam for exam, rectal exam, pelvic exam for females, prostate exam for malesfemales, prostate exam for males
Age-appropriate cancer screening – Age-appropriate cancer screening – MMG, Pap smear, colonoscopy, PSAMMG, Pap smear, colonoscopy, PSA
Do not recommend CT scans, etc.Do not recommend CT scans, etc. Chest x-ray is reasonableChest x-ray is reasonable
Was VTE “provoked”?Was VTE “provoked”?
CBC with diffCBC with diff CMPCMP UrinalysisUrinalysis Fecal occult blood testFecal occult blood test
Inherited Inherited thrombophiliathrombophilia Factor V Leiden (2.2)Factor V Leiden (2.2) Prothrombin gene mutation (2.8)Prothrombin gene mutation (2.8) Protein C deficiency (7.3)Protein C deficiency (7.3) Protein S deficiency (8.5)Protein S deficiency (8.5) Antithrombin III deficiency (8.1)Antithrombin III deficiency (8.1)
Acquired – antiphospholipid antibody Acquired – antiphospholipid antibody syndrome (APS)syndrome (APS)
Who to testWho to test
<45 years old with unprovoked <45 years old with unprovoked venous or arterial thromboembolic venous or arterial thromboembolic diseasedisease
>>2 idiopathic thrombotic episodes 2 idiopathic thrombotic episodes Thrombosis in unusual site Thrombosis in unusual site VTE & strong family history of VTEVTE & strong family history of VTE History of recurrent fetal lossHistory of recurrent fetal loss ? VTE in reproductive age female? VTE in reproductive age female
Unusual sitesUnusual sites
Cerebral veinsCerebral veins IVC, renal veinsIVC, renal veins Mesenteric veinsMesenteric veins Portal and hepatic veinsPortal and hepatic veins
Recurrent fetal lossRecurrent fetal loss
Unexplained death at Unexplained death at >>10 10 weeks gestation–weeks gestation–morphologically normalmorphologically normal
Three or more 1st-trimester Three or more 1st-trimester pregnancy losses without an pregnancy losses without an intercurrent term pregnancyintercurrent term pregnancy
Who to testWho to test
What about a strong family history What about a strong family history without personal history of VTE?without personal history of VTE?
Test affected family member firstTest affected family member first If history is very suggestive of If history is very suggestive of
inherited thrombophilia and there inherited thrombophilia and there is no affected family member alive is no affected family member alive to be tested – needs appropriate to be tested – needs appropriate counselingcounseling
Hypercoagulable Hypercoagulable Work-upWork-up ““Hypercoag panel”Hypercoag panel”
-Protein C, protein S, AT III (functional)-Protein C, protein S, AT III (functional)
-Lupus anticoagulant-Lupus anticoagulant
-APC resistance-APC resistance Factor V Leiden (if APC resistance Factor V Leiden (if APC resistance
low)low) Prothrombin gene mutationProthrombin gene mutation Anticardiolipin antibodiesAnticardiolipin antibodies
Timing of testsTiming of tests
Factor V Leiden and prothrombin Factor V Leiden and prothrombin mutation can be checked at any timemutation can be checked at any time
Wait at least 4-6 weeks after acute Wait at least 4-6 weeks after acute event to check lupus anticoagulant event to check lupus anticoagulant and cardiolipin antibodies (or later)and cardiolipin antibodies (or later)
Most efficient to check all other tests Most efficient to check all other tests >>2 weeks after course of 2 weeks after course of anticoagulation is completedanticoagulation is completed
Timing of TestsTiming of Tests
In setting of acute VTE, proteins C & In setting of acute VTE, proteins C & S and AT III may be decreasedS and AT III may be decreased
Cardiolipin antibodies may be Cardiolipin antibodies may be present as an acute phase reactantpresent as an acute phase reactant
Heparin interferes with AT III activity Heparin interferes with AT III activity and lupus anticoagulant assaysand lupus anticoagulant assays
Coumadin lowers proteins C & SCoumadin lowers proteins C & S
Timing of TestsTiming of Tests
In acute phase, if protein C or S is In acute phase, if protein C or S is normal, that test does not need to be normal, that test does not need to be repeated repeated
Some evidence that coumadin may Some evidence that coumadin may increase AT III levels – if AT III is at increase AT III levels – if AT III is at low end of normal range, then test low end of normal range, then test needs to be repeated off coumadinneeds to be repeated off coumadin
Never need to repeat FVL or PTM testNever need to repeat FVL or PTM test
Antiphospholipid Antiphospholipid Antibody Syndrome Antibody Syndrome (APS)(APS) Clinical criteria: One or more Clinical criteria: One or more
episodes of venous, arterial, or small episodes of venous, arterial, or small vessel thrombosis and/or morbidity vessel thrombosis and/or morbidity with pregnancywith pregnancy
Laboratory criteria: Presence of anti-Laboratory criteria: Presence of anti-phospholipid antibodies on 2 or more phospholipid antibodies on 2 or more occasions at least 12 weeks apart occasions at least 12 weeks apart and and <<5y prior to clinical 5y prior to clinical manifestationsmanifestations
APS Clinical CriteriaAPS Clinical Criteria
Imaging or histologic evidence of Imaging or histologic evidence of thrombosis in any tissue or organthrombosis in any tissue or organ
Fetal death at Fetal death at >>10 wks gestation10 wks gestation Premature birth before 34 weeks Premature birth before 34 weeks
because of eclampsia, because of eclampsia, preeclampsia or placental preeclampsia or placental insufficiencyinsufficiency
>>3 pregnancy losses <10 weeks3 pregnancy losses <10 weeks
APS Laboratory APS Laboratory CriteriaCriteria Positive lupus anticoagulantPositive lupus anticoagulant Moderate or high titer IgG and/or Moderate or high titer IgG and/or
IgM anticardiolipin antibodiesIgM anticardiolipin antibodies IgG or Ig M antibodies to beta2-IgG or Ig M antibodies to beta2-
glycoprotein-1glycoprotein-1 On two or more occasions at On two or more occasions at
least 12 weeks apartleast 12 weeks apart
Antiphospholipid Antiphospholipid Antibody SyndromeAntibody Syndrome VTEVTE Stroke, white matter lesionsStroke, white matter lesions MI, nonbacterial endocarditisMI, nonbacterial endocarditis Renal failureRenal failure Thrombocytopenia, TTP/HUSThrombocytopenia, TTP/HUS
Livedo reticularisLivedo reticularis
Catastrophic APSCatastrophic APS
Involvement of 3 or more organs, Involvement of 3 or more organs, systems, or tissuessystems, or tissues
Develop simultaneously or in <1 Develop simultaneously or in <1 weekweek
Histopathologic evidence of small Histopathologic evidence of small vessel occlusionvessel occlusion
Presence of antiphospholipid Presence of antiphospholipid antibodiesantibodies
Asherson et al., Lupus, 2003, 12:530Asherson et al., Lupus, 2003, 12:530
Catastrophic APSCatastrophic APS
Treatment of underlying illnessTreatment of underlying illness Heparin acutely then warfarinHeparin acutely then warfarin High dose steroidsHigh dose steroids Plasma exchange +/- IVIG if there Plasma exchange +/- IVIG if there
is evidence of TTP/HUSis evidence of TTP/HUS For survivors, lifelong warfarinFor survivors, lifelong warfarin
AnticoagulationAnticoagulation
Low molecular weight heparin Low molecular weight heparin acutely until INR therapeutic for 2 acutely until INR therapeutic for 2 daysdays
Warfarin for 3-6 monthsWarfarin for 3-6 months INR 2.0-3.0INR 2.0-3.0 For idiopathic DVT or inherited For idiopathic DVT or inherited
thrombophilia can discuss prolonged thrombophilia can discuss prolonged therapy – delays risk of recurrencetherapy – delays risk of recurrence
What is this? What is this? Why does it happen?Why does it happen?
Warfarin skin necrosisWarfarin skin necrosis
Protein C deficiencyProtein C deficiency Vitamin K dependent protein with Vitamin K dependent protein with
relatively short half-liferelatively short half-life Start warfarin after full Start warfarin after full
heparinization documented by PTT heparinization documented by PTT or anti-Xa assay or anti-Xa assay
Start at a low dose (2 mg a day) Start at a low dose (2 mg a day) then gradually increasethen gradually increase
Warfarin skin necrosisWarfarin skin necrosis
Stop warfarinStop warfarin Give vitamin KGive vitamin K HeparinizeHeparinize Consider protein C administration Consider protein C administration
(FFP, (FFP, protein C concentrateprotein C concentrate)) Can retreat with warfarin in Can retreat with warfarin in
setting of protein C administrationsetting of protein C administration
AT III deficiencyAT III deficiency
Sometimes show resistance to Sometimes show resistance to heparinheparin
May require larger dosesMay require larger doses Consider antithrombin concentrateConsider antithrombin concentrate
-Unusually severe thrombosis-Unusually severe thrombosis
-Recurrent thrombosis in setting of -Recurrent thrombosis in setting of adequate anticoagulationadequate anticoagulation
-Inability to adequately anticoagulate-Inability to adequately anticoagulate
Discussion of lifelong Discussion of lifelong anticoagulationanticoagulation Recurrent idiopathic VTERecurrent idiopathic VTE Idiopathic life-threatening VTEIdiopathic life-threatening VTE Antiphospholipid antibody Antiphospholipid antibody
syndrome (with persistently syndrome (with persistently elevated antibodies)elevated antibodies)
Antithrombin III deficiencyAntithrombin III deficiency Homozygous or compound Homozygous or compound
heterozygous defectsheterozygous defects
Inherited Inherited thrombophilia & thrombophilia & surgical prophylaxissurgical prophylaxis Consider as “high risk” groupConsider as “high risk” group Exception may be Factor V Leiden Exception may be Factor V Leiden
– prophylaxis based on risk of – prophylaxis based on risk of surgerysurgery
AT III deficiency – could consider AT III deficiency – could consider antithrombin concentrate antithrombin concentrate (retrospective & case reports (retrospective & case reports only) only)
Inherited Inherited thrombophilia and thrombophilia and pregnancypregnancy Anticoagulate during pregnancy Anticoagulate during pregnancy
and 6 weeks post-partumand 6 weeks post-partum AT III deficiency, homozygous FVL AT III deficiency, homozygous FVL
or PTM, compound heterozygotes or PTM, compound heterozygotes Personal history of VTE or strong Personal history of VTE or strong
family history of VTE use family history of VTE use therapeutic dose, otherwise therapeutic dose, otherwise prophylactic dose prophylactic dose
Inherited Inherited thrombophilia and thrombophilia and pregnancypregnancy Heterozygous FVL or PTM, protein C Heterozygous FVL or PTM, protein C
or S deficiencyor S deficiency Prophylaxis if personal history of VTEProphylaxis if personal history of VTE Consider if 1Consider if 1stst degree relative with degree relative with
VTE at age <50VTE at age <50 If no prior history of VTE then only If no prior history of VTE then only
postpartum prophylaxis if C-sectionpostpartum prophylaxis if C-section
Should family Should family members be tested?members be tested? Need to be counseled on how Need to be counseled on how
result will be usedresult will be used Females of reproductive ageFemales of reproductive age Protein C deficiencyProtein C deficiency If there is more than one inherited If there is more than one inherited
thrombophilia in the familythrombophilia in the family Usually we doUsually we do
When to refer to When to refer to HematologyHematology Inherited thrombophilia with VTEInherited thrombophilia with VTE Recurrent idiopathic VTE without Recurrent idiopathic VTE without
inherited thrombophiliainherited thrombophilia Contemplating lifelong Contemplating lifelong
anticoagulationanticoagulation Patient requestPatient request
Questions?Questions?