Antiphospholipid Antibody Syndrome and Pregnancy Lavenia B.

Carpenter MD Basics Description An autoimmune syndrome characterized by recurrent venous/arterial thromboembolic disease and/or pregnancy morbidity in the orm o recurrent etal loss or premature birth in association !ith persistently positive aPL. "ypes#
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Primary# Patients !ithout clinical evidence o another autoimmune disease Secondary# Patients !ith evidence o another autoimmune disease such as SL$

Spectrum o illness#
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Asymptomatic aPL positivity#

%ot APS %o treatment

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Pregnancy morbidity only &ascular events#

D&"' arterial thrombosis' P$' "(A' stro)e' renal in arction' etc.

%onthrombotic mani estations#

*aynaud phenomenon' livedo reticularis' cardiac valvular abnormalities' thrombocytopenia' transverse myelitis' multiple sclerosis+li)e disease

Catastrophic APS#

Severe disseminated vascular occlusions Multiorgan ischemia and in arction

,eriatric Considerations Loo) or other causes o thromboembolic events in this age group. Pediatric Considerations Suspect in young patients !ith "(A/stro)e -/. o children !ith idiopathic cerebral ischemia and acute in arction have evidence o elevated aPL antibodies.

/actor & Leiden heterozygosity *etinal vaso0occlusion

Pregnancy Considerations

Pregnancy loss at all stages Placental dys unction in the .rd trimester (1,* Preeclampsia

$pidemiology aPL antibodies are present' at some point' in almost every individual. Clinical criteria and persistently positive aPLs are re2uired or diagnosis.

345 present !ith primary orm.

(ncidence 635 o recurrent pregnancy loss .35 !ith primary disease have cardiac valvular abnormalities

345 !ith SL$ and APS have evidence o valvular abnormality

Prevalence 6+35 healthy young adults have aPLs 3457 o patients !ith SL$ !ith positive aPLs !ill develop this syndrome. *is) /actors /amily history o autoimmune disease /amily history o aPL positivity

Personal history o thrombosis (n ection induction

,enetics 1n)no!n 8LA class (( polymorphism and induction o aPL9

:-0,lycoprotein ( co actor or aPL binding associated !ith clinical mani estation o disease gene located on chromosome 6;

Pathophysiology Any organ can be involved. "hrombosis is the primary etiology o all nonpregnancy mani estations#
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Activation o endothelial cells' o<idant mediated in=ury o the vascular endothelium' inter erence !ith phospholipid binding proteins#

(ntercellular adhesion molecule06' vascular cell adhesion molecule06' and P0selectin Disruption o the anne<in0& shield around cells and trophoblasts (nter erence !ith protein C antithrombotic path!ay

Complement activation

(nter erence !ith prostacyclin thrombo<ane balance#

(nhibition o AA release AA essential or prostacyclin production Prostacyclin potent vasodilator and inhibitor o thrombo<ane aggregation

A ects the adhesion molecules bet!een trophoblastic elements o syncytiotrophoblast#

Damage unrelated to thrombosis

Associated Conditions SL$ *aynaud phenomenon

Malignant 8"% %ephrotic syndrome Cardiac valvular abnormalities

Diagnosis Sapporo criteria or diagnosis# Clinical criteria >at least 6 o ollo!ing?# o &ascular thrombosis#

@6 clinical episodes o arterial' venous' or small vessel thrombosis occurring !ithin any tissue or organ

Complication o pregnancy#

@6 une<plained deaths o morphologically normal etuses at or a ter the 64th !ee) o pregnancy A* @6 premature births o morphologically normal neonates at or be ore the .Bth !ee) o pregnancy A* @. une<plained spontaneous abortions be ore the 64th !ee) o pregnancy

A%D at least 6 laboratory criterion#

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Anticardiolipin (g, or (gM antibodies present in moderate or high levels in the blood on @- occasions at least C !ee)s apart Lupus anticoagulant detected in the blood on @- occasions at least C !ee)s apart

Signs and Symptoms

Arthralgias "hrombosis Livedo reticularis /amily history o connective tissue disease Patient history o thromboembolic disease Pregnancy morbidity#
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8istory

Prior pregnancy loss or preterm delivery 8istory o preeclampsia

Physical $<am $vidence o thromboembolic disease D&" most common initial mani estation o the disease "ests

$L(SA test or anticardiolipin antibodies# o (g,' (gM' (gA

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(g, most predictive

Clotting test or lupus anticoagulant :-0,lycoprotein 6 may be in uture screens Labs are poorly standardized and lead to !idely ranging aPL levels. "hrombocytopenia Leu)openia

Lab

P.B.; "reatment ,eneral Measures *is) modi ication# o Smo)ing cessation

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Control o 8"%' diabetes' hyperlipidemia Avoid ACP use

Prophyla<is during high0ris) periods >surgery' immobilization' pregnancy?

Pregnancy0Speci ic (ssues Pregnancy !ith history o recurrent etal loss# Aspirin D6 mg/d prior to conception or at con irmation o pregnancy

18 3'444+64'444 1 SC b.i.d. vs. LME8 prophyla<is#

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More studies e<ist on 18 %ot enough data to determine bene it o 6 over the other

Start at con irmation o etal cardiac activity

P.B.D By "rimester 6st trimester# Start heparin and aspirin !hen etal cardiac activity detected >consider aspirin sooner' but not heparin because o ris) or osteoporosis? -nd trimester# Continue aspirin and heparin

.rd trimester# Continue heparin and aspirinF discontinue both =ust be ore delivery Postpartum# D&" prophyla<is' therapeutic anticoagulation in mothers !ith a history o prior thrombosis

*is)s or Mother "hrombosis Preeclampsia *is)s or /etus Preterm delivery /etal gro!th restriction

Death

Medication >Drugs? %onpregnant# Ear arin treatment o moderate intensity >to achieve an (%* o -.4+..4? signi icantly reduces the rate o recurrent thrombosis# o Duration o treatment is li elong.

Corticosteroids and azathioprine or treatment o symptoms o lupus in patients !ith secondary orm o the syndrome (n patients !ho develop ne! thromboses despite moderate0intensity anticoagulant therapy and or patients !ith catastrophic APS#
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Plasmapheresis (& immunoglobulin

/ollo!up Disposition (ssues or *e erral *heumatologic !or)up

Anticoagulation monitoring and duration

Prognosis Pulmonary 8"%' neurologic involvement' myocardial ischemia' nephropathy' gangrene o e<tremities' and catastrophic APS are associated !ith a !orse prognosis. Most patients e<perience recurrences months or years a ter the initial event.

Mortality rate is G345 in patients presenting !ith the catastrophic type' and death is due to multiorgan system ailure.

Complications Discontinuation o !ar arin results in increased ris) o thromboembolic disease' particularly in the 6st C months a ter stopping treatment. "herapeutic anticoagulation is recommended in postpartum period or all !omen !ith history o thromboembolic disease. Patient Monitoring As !ar arin therapy is li elong' patients must have regular monitoring to maintain (%* in the therapeutic range >bet!een -.4 and ..4?. Bibliography Alarcon0Segovia D' et al. Prophyla<is o the antiphospholipid syndrome# A consensus report. Lupus. -44.F6->;?#BHH+34.. Carp 8. Antiphospholipid syndrome in pregnancy. Curr Apin Abstet ,ynecol. -44BF6C#6-H+6.3. /rancis I' et al. (mpaired e<pression o endometrial di erentiation mar)ers and complement regulatory proteins in patients !ith recurrent pregnancy loss associated !ith antiphospholipid syndrome. Molecul 8uman *eprod. -44CF6->;?#B.3+BB-. Lim E' et al. Management o antiphospholipid antibody syndrome. IAMA. -44CF-H3#6434+643;. %oble L' et al. Antiphospholipid antibodies associated !ith recurrent pregnancy loss# Prospective' multicenter' controlled pilot study comparing treatment !ith lo! molecular !eight heparin versus un ractionated heparin. /ertil Steril. -443FD.>.?#CDB+ CH4. "incani A' et al. "reatment o pregnant patients !ith antiphospholipid syndrome. Lupus. -44.F6->;?#3-B+3-H. Miscellaneous Clinical Pearls J Li)e any autoimmune disease' APS can have a !ide range o presentations depending on the organ system primarily e ected. J (n pregnancy' thrombosis may be secondary to dys unctional trophoblast invasion or recurrent pregnancy loss. J APS is still poorly understood and research is needed on the appropriate treatmentF !atch current literature. Abbreviations J AAKArachidonic acid J aPLKAntiphospholipid antibodies J APSKAntiphospholipid antibody syndrome J D&"KDeep venous thrombosis J $L(SAK$nzyme0lin)ed immunosorbent assay

J (1,*K(ntrauterine gro!th restriction J LME8KLo! molecular !eight heparin J ACPKAral contraceptive pill J P$KPulmonary embolism J SL$KSystemic lupus erythematosus J "(AK"ransient ischemic attac) J 18K1n ractionated heparin Codes (CDH0CM J ;H3.;H Ather' unspeci ied' nonspeci ic' immunologic inding J -DC.H Ather' unspeci ied' coagulation de ect Patient "eaching Prevention J *is) modi ication# + Smo)ing cessation + Control o 8"%' diabetes' hyperlipidemia + Avoid ACP use + Prophyla<is during high0ris) periods >surgery' immobilization' pregnancy? J Pregnancy !ith history o recurrent etal loss# + Aspirin D6 mg/d prior to conception or at con irmation o pregnancy + 18 3'444+64'444 1 SC b.i.d. vs. LME8 prophyla<is# J More studies !ith 18 J %ot enough data to determine bene it o 6 over the other J Start at con irmation o etal cardiac activity