Interdepartment Wafarin

Interdepartment conferenceInterdepartment conference

4 Feb 20104 Feb 2010

ผูป้่วยหญิงไทยคู่ อายุผูป้่วยหญิงไทยคู่ อายุ 51 51 ปป ีี 22ndnd admission admission ที่ที่รพรพ..จุฬาจุฬา

CC : CC : สับสนสับสน 1 d PTA1 d PTA

PI : 1 d PTA PI : 1 d PTA สามีผู้ปว่ยสงัเกตว่าผูป้่วยดูสับสน สามีผู้ปว่ยสงัเกตว่าผูป้่วยดูสับสน พูดคยุไม่รู้เรื่อง ทำาตามที่บอกไม่ได้ แขนขาดูพูดคยุไม่รู้เรื่อง ทำาตามที่บอกไม่ได้ แขนขาดูอ่อนแรงมากกว่าเดิมทั้งสองข้างอ่อนแรงมากกว่าเดิมทั้งสองข้าง

PH : PH : CA cervix stage II CA cervix stage II ได้รับการผ่าตัดที่รพได้รับการผ่าตัดที่รพ..หัวเฉียวหัวเฉียว 14 years 14 years

PTAPTA Antiphospholipid syndrome Antiphospholipid syndrome มาด้วยแขนขาข้างซ้ายไม่มีมาด้วยแขนขาข้างซ้ายไม่มี

แรง หน้าเบี้ยวแรง หน้าเบี้ยว large infarction of right MCA large infarction of right MCA

work up : anticardiolipin IgG + ( at 2546 and 2549)work up : anticardiolipin IgG + ( at 2546 and 2549)

Status Status เดิม แขนขาข้างซ้ายอ่อนแรง แต่สามารถเดินไปเดิม แขนขาข้างซ้ายอ่อนแรง แต่สามารถเดินไปมาได้เอง พูดคุยรู้เรื่องดีมาได้เอง พูดคุยรู้เรื่องดี

Clinical criteriaClinical criteria

1. Vascular thrombosis1. Vascular thrombosis One or more clinical episodes of arterial, One or more clinical episodes of arterial,

venous, or small vessel thrombosis, in any venous, or small vessel thrombosis, in any tissue or organ. tissue or organ.

Thrombosis must be confirmed by objective Thrombosis must be confirmed by objective validated criteria (i.e. unequivocal findings of validated criteria (i.e. unequivocal findings of appropriate imaging studies or appropriate imaging studies or histopathology). histopathology).

For histopathologic confirmation, thrombosis For histopathologic confirmation, thrombosis should be present without significant evidence should be present without significant evidence of inflammation in the vessel wall.of inflammation in the vessel wall.

Journal of Thrombosis and Haemostasis, 4: 295–306Journal of Thrombosis and Haemostasis, 4: 295–306

Pregnancy morbidityPregnancy morbidity (a) One or more unexplained deaths of a (a) One or more unexplained deaths of a

morphologically normal fetus at or beyond the 10th morphologically normal fetus at or beyond the 10th week of gestation, with normal fetal morphology week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of documented by ultrasound or by direct examination of the fetus, orthe fetus, or

(b) One or more premature births of a morphologically (b) One or more premature births of a morphologically normal neonate before the 34th week of gestation normal neonate before the 34th week of gestation because of: because of: (i) eclampsia or severe preeclampsia defined (i) eclampsia or severe preeclampsia defined

according to standard definitions , or according to standard definitions , or (ii) recognized features of placental insufficiency, (ii) recognized features of placental insufficiency,

oror


(c) Three or more unexplained (c) Three or more unexplained consecutive spontaneous abortions consecutive spontaneous abortions before the 10th week of gestation, with before the 10th week of gestation, with maternal anatomic or hormonal maternal anatomic or hormonal abnormalities and paternal and maternal abnormalities and paternal and maternal chromosomal causes excluded.chromosomal causes excluded.


Laboratory criteriaLaboratory criteria

1. Lupus anticoagulant (LA) present in 1. Lupus anticoagulant (LA) present in plasma, on two or more occasions at least plasma, on two or more occasions at least 12 weeks apart, detected according to the 12 weeks apart, detected according to the guidelines of the International Society on guidelines of the International Society on Thrombosis and Haemostasis (Scientific Thrombosis and Haemostasis (Scientific Subcommittee on LAs/phospholipid-Subcommittee on LAs/phospholipid-dependent antibodies)dependent antibodies)


2. Anticardiolipin (aCL) antibody of IgG 2. Anticardiolipin (aCL) antibody of IgG and/or IgM isotype in serum or plasma, and/or IgM isotype in serum or plasma, present in medium or high titer (i.e. >40 present in medium or high titer (i.e. >40 GPL or MPL, or >the 99th percentile), on GPL or MPL, or >the 99th percentile), on two or more occasions, at least 12 weeks two or more occasions, at least 12 weeks apart, measured by a standardized ELISA apart, measured by a standardized ELISA


3. Anti-b2 glycoprotein-I antibody of IgG 3. Anti-b2 glycoprotein-I antibody of IgG and/or IgM isotype in serum or plasma (in and/or IgM isotype in serum or plasma (in titer >the 99th percentile), present on two titer >the 99th percentile), present on two or more occasions, at least 12 weeks or more occasions, at least 12 weeks apart, measured by a standardized ELISA, apart, measured by a standardized ELISA, according to recommended proceduresaccording to recommended procedures


Antiphospholipid antibody syndrome Antiphospholipid antibody syndrome (APS) is present if at least one of the (APS) is present if at least one of the clinical criteria and one of the laboratory clinical criteria and one of the laboratory criteria that follow are metcriteria that follow are met

Classification of APS should be avoided if Classification of APS should be avoided if less than 12 weeks or more than 5 years less than 12 weeks or more than 5 years separate the positive aPL test and the separate the positive aPL test and the clinical manifestation.clinical manifestation.


Current medicationCurrent medication Warfarin (3) 1x1 po OD except Warfarin (3) 1x1 po OD except จจ, , พฤพฤ

Warfarin (3)Warfarin (3) ½ x1 (total 18 mg/week)½ x1 (total 18 mg/week) Amlodipine (5) ½ x1Amlodipine (5) ½ x1 Simvastatin (10) 1x1Simvastatin (10) 1x1 Neurontin (300) 1x2Neurontin (300) 1x2

Last INR 2.9 (28/12/2552)Last INR 2.9 (28/12/2552)

Physical examinationPhysical examination

GA : middle age Thai female, alert but not GA : middle age Thai female, alert but not cooperative cooperative

V/S : BP 140/90 mmHg PR 80 /min regularV/S : BP 140/90 mmHg PR 80 /min regular RR 16 /min BT 37 °c RR 16 /min BT 37 °c HEENT : Not pale, no icteric scleraHEENT : Not pale, no icteric sclera No carotid bruitNo carotid bruit Heart : normal S1 S2, no murmurHeart : normal S1 S2, no murmur Lung : clearLung : clear

Abdomen : soft, not tenderAbdomen : soft, not tender no hepatosplenomegalyno hepatosplenomegaly Neuro : Neuro : รู้ตวั ไม่ทำำตำมสัง่ รู้ตวั ไม่ทำำตำมสัง่ Lt facial weakness, UMNLt facial weakness, UMN motor IV IImotor IV II IV IIIIV III DTR 3+ 4+DTR 3+ 4+ BBK ↓ ↑BBK ↓ ↑

CT brainCT brain

CT brain without contrastCT brain without contrast

3.6x3.6 cm round shaped extra axial lesion with 3.6x3.6 cm round shaped extra axial lesion with hyperdense rim at left frontoparietal region with hyperdense rim at left frontoparietal region with intralesional hypodenxe-hyperdense fluid level , intralesional hypodenxe-hyperdense fluid level , possibly multistage of extra axial hematomapossibly multistage of extra axial hematoma

Lens-shaped extraaxial hyperdense lesion at left Lens-shaped extraaxial hyperdense lesion at left frontal and left parieto-temporal region with frontal and left parieto-temporal region with maximal thickness measured about 1 cm maximal thickness measured about 1 cm

Crescent shaped extraaxial mixed hyper-Crescent shaped extraaxial mixed hyper-hypodense lesion at left frontal region , hypodense lesion at left frontal region , acute to subacute subdural hematomaacute to subacute subdural hematoma

Hyperdensity along anterior and posterior Hyperdensity along anterior and posterior interhemispheric fissure and left tentorial interhemispheric fissure and left tentorial cerebelli, subarachnoid hemorrhagecerebelli, subarachnoid hemorrhage

Laboratory Laboratory

CBC : Hb 10.5 Hct 32.0% (MCV 81 RDW CBC : Hb 10.5 Hct 32.0% (MCV 81 RDW 13.7) WBC 9850 (N84 L 11.6) Plt 23000013.7) WBC 9850 (N84 L 11.6) Plt 230000

PT 63.7 INR 5.9PT 63.7 INR 5.9

Management Management

Blood Reviews(2009) 23,1–9Blood Reviews(2009) 23,1–9

Vitamin KVitamin K

It takes at least 2 to 6 hours, and often It takes at least 2 to 6 hours, and often more than 24 hours, to achieve an more than 24 hours, to achieve an effective response to vitamin K effective response to vitamin K administrationadministration

Necessary to achieve a sustained reversal Necessary to achieve a sustained reversal of anticoagulationof anticoagulation

Stroke 2006;37;256-262Stroke 2006;37;256-262

The small risk of anaphylaxis associated The small risk of anaphylaxis associated with the intravenous preparationwith the intravenous preparation

Subcutaneous administration may be Subcutaneous administration may be safer but does not correct the INR as safer but does not correct the INR as rapidly or as reliably as intravenous userapidly or as reliably as intravenous use

The time of onset of oral vitamin K is too The time of onset of oral vitamin K is too slow to be therapeutically useful in this slow to be therapeutically useful in this situation.situation.

Stroke 2006;37;256-262Stroke 2006;37;256-262


Fresh Frozen PlasmaFresh Frozen Plasma

FFP contains all coagulation factors in a FFP contains all coagulation factors in a nonconcentrated formnonconcentrated form

Achieve effective hemostasis a large Achieve effective hemostasis a large volume (up to several liters) is required.volume (up to several liters) is required.

It acts more quickly than vitamin K, though It acts more quickly than vitamin K, though it has a shorter half-life.it has a shorter half-life.

Stroke 2006;37;256-262Stroke 2006;37;256-262

Factor IX levels may remain low despite Factor IX levels may remain low despite adequate correction of other factors, thus adequate correction of other factors, thus leading to incomplete haemostasis.leading to incomplete haemostasis.


Prothrombin complex Prothrombin complex concentratesconcentrates

PCC contain varying combination of PCC contain varying combination of coagulation factors VII, IX, X, and coagulation factors VII, IX, X, and prothrombin as well as proteins C, S and Z prothrombin as well as proteins C, S and Z in a concentrated form in a concentrated form

Stroke 2006;37;256-262Stroke 2006;37;256-262

Am.J.Hematol.83:137–143,2008.Am.J.Hematol.83:137–143,2008.

No prospective randomised controlled trial No prospective randomised controlled trial in OAT-related ICH comparing FFP and in OAT-related ICH comparing FFP and PCC comparing haematoma growth and PCC comparing haematoma growth and functional outcomefunctional outcome


Am.J.Hematol.83:137–143,2008.Am.J.Hematol.83:137–143,2008.

Recombinant activated Recombinant activated factor VIIafactor VIIa

A recent clinical trial in acute SICH A recent clinical trial in acute SICH without without coagulopathycoagulopathy demonstrated that rFVIIa demonstrated that rFVIIa reduced hematoma growthreduced hematoma growth

But did not improve survival or functional But did not improve survival or functional outcome after intracerebral hemorrhage.outcome after intracerebral hemorrhage.

Stroke 2006;37;256-262Stroke 2006;37;256-262

NEJM 2008;358:2127-37NEJM 2008;358:2127-37

There was There was no significantno significant difference between the difference between the groups receiving rFVIIa and the placebo groupgroups receiving rFVIIa and the placebo group

NEJM 2008;358:2127-37NEJM 2008;358:2127-37

P<0.04

NEJM 2008;358:2127-37NEJM 2008;358:2127-37

There are limited data regarding the use of There are limited data regarding the use of rFVIIa in OAT-ICH.rFVIIa in OAT-ICH.

Treatment with rFVIIa may have lead to a Treatment with rFVIIa may have lead to a faster correction of INR or decreased FFP faster correction of INR or decreased FFP requirementsrequirements

Stroke 2006;37;256-262Stroke 2006;37;256-262

Ann Intern Med. 2002;137:884-888Ann Intern Med. 2002;137:884-888

None of the patients died and there were None of the patients died and there were no signs of thrombosis.no signs of thrombosis.

In all cases the neurosurgeon assessed In all cases the neurosurgeon assessed the hemostasis better than expected.the hemostasis better than expected.

Guideline Guideline


Time Window for TreatmentTime Window for Treatment

In OAT-ICH, the natural course of In OAT-ICH, the natural course of hematoma expansion is probably more hematoma expansion is probably more prolonged, perhaps up to 24 or 48 hoursprolonged, perhaps up to 24 or 48 hours

Patients presenting as late as 24 hours (or Patients presenting as late as 24 hours (or even later) may benefit from effective even later) may benefit from effective hemostatic treatment.hemostatic treatment.

Monitoring HemostasisMonitoring Hemostasis

PT/INR : The test is sensitive to PT/INR : The test is sensitive to decreased levels of factor VII andf actorX, decreased levels of factor VII andf actorX, and prothrombin, but not to decreased and prothrombin, but not to decreased levels of factor IXlevels of factor IX

INR values should be interpreted with INR values should be interpreted with caution as they might not reflect the actual caution as they might not reflect the actual status of all vitamin K–dependent status of all vitamin K–dependent coagulation factorscoagulation factors

ThromboelastographyThromboelastography

Vit K 10 mg IV statVit K 10 mg IV stat FFP 4 unit IV dripFFP 4 unit IV drip

Repeat coagulagram after administer Repeat coagulagram after administer vitamin K and FFP vitamin K and FFP

PTT 33.2PTT 33.2 PT 13.6PT 13.6 INR 1.2INR 1.2

Conservative treatmentConservative treatment Observe neurological sign Observe neurological sign stable stable

Admission day 11Admission day 11 ขาข้างซ้ายบวมขึ้น ไม่ร้อนขาข้างซ้ายบวมขึ้น ไม่ร้อน PE : O2 sat room air 98% PE : O2 sat room air 98% Heart & Lung : normalHeart & Lung : normal Leg : Right calf 33 cm / Left calf 35 cm Leg : Right calf 33 cm / Left calf 35 cm pitting edema left leg pitting edema left leg no superficial vein dilatedno superficial vein dilated Homan’s sign negativeHoman’s sign negative

U/S dopplerU/S doppler

Echogenic thrombus partially filled in left SFV, Echogenic thrombus partially filled in left SFV, extend to left popliteal vein causing decreased extend to left popliteal vein causing decreased flow of these veins. Loss of compressibility of flow of these veins. Loss of compressibility of mentioned vein is also notedmentioned vein is also noted

Imp : recent thrombosis of left SFV extends to Imp : recent thrombosis of left SFV extends to left popliteal veinleft popliteal vein

D-dimer = 5501D-dimer = 5501

CT brain CT brain

Interval decrease of subdural hematoma, Interval decrease of subdural hematoma, epidural hematomaepidural hematoma

No new intracranial hemorrhagic clotNo new intracranial hemorrhagic clot

Management Management

Fatal PEFatal PE Recurrent ICHRecurrent ICH

Inferior vena cava filtersInferior vena cava filters

IndicationIndication Absolute contraindication to anticoagulationAbsolute contraindication to anticoagulation Failure of anticoagulationFailure of anticoagulation

StrokeStroke. . 2003;34:2999-30052003;34:2999-3005


Untreat DVT Untreat DVT Fatal PE 16.2% Fatal PE 16.2% Treat DVT Treat DVT Fatal PE 0.7%. Fatal PE 0.7%.

StrokeStroke. . 2003;34:2999-30052003;34:2999-3005


No studies IVC filters alone compare anticoagulantNo studies IVC filters alone compare anticoagulant

StrokeStroke. . 2003;34:2999-30052003;34:2999-3005


Risk of recurrent ICH associatedRisk of recurrent ICH associatedwith anticoagulants unknown with anticoagulants unknown

StrokeStroke. . 2003;34:2999-30052003;34:2999-3005

Unselected patient Unselected patient Lobar Lobar recurrent ICH 1 recurrent ICH 1 %% Non lobar Non lobar recurrent ICHrecurrent ICH 0.5 0.5 %%


StrokeStroke. . 2003;34:2999-30052003;34:2999-3005

Major hemorrhageMajor hemorrhageEnoxaprin (1.5 mg/kg) OD x 3 month Enoxaprin (1.5 mg/kg) OD x 3 month 10.5 % 10.5 %Warfarin x 3 month Warfarin x 3 month 21.1% 21.1% p p = 0.09= 0.09

(The Neurologist 2009;15: 329–331)(The Neurologist 2009;15: 329–331)

Enoxaprin 40mg/day after 48 hr ICH Vs Enoxaprin 40mg/day after 48 hr ICH Vs Long compression stockingLong compression stocking

F/U CT day 3, 7, 21 F/U CT day 3, 7, 21 no hematoma enlargement no hematoma enlargement

(The Neurologist 2009;15: 329–331)(The Neurologist 2009;15: 329–331)

In this patientIn this patient Enoxaparin 0.4 cc SC ODEnoxaparin 0.4 cc SC OD Observe neurological signObserve neurological sign

DischargeDischarge

Interdepartment Wafarin

Health & Medicine

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