ORI GI N AL ARTI CLE
Deep vein t hrom bosis during pregna ncy w ork up
Jorge Agle Ka lilI, M a r co Ant onio C. JovinoI I; M a r ce lo Ar r ia ga de Lim aI I; Rena t o Ka lilI I I; M a r ia Elisa Ruffolo M a glia r iI V; M a r ce lo K. D i Sa nt oV
IHead physician, Vascular Surgery Service, Hospit al e Mat ernidade São Luiz ( HMSL) , São Paulo, SP, Brazil.
I IVascular surgeon, HMSL, São Paulo, SP, Brazil.
I I IObst et rician and Gynecologist , HMSL, São Paulo, SP, Brazil.
I VMSc. Assist ant t eaching professor, Medical Clinic Service, Depart m ent of Medicine, Faculdade de Ciências Médicas, Sant a Casa de São Paulo, São Paulo, SP, Brazil.
VMedical st udent ( sixt h year) , Faculdade de Ciências Médicas de Sant os, Sant os, SP, Brazil.
Correspondence
J Vasc Bras. 2008; 7( 1) : 28- 37.
ABSTRACT
Ba ck ground: Deep venous t hrom bosis ( DVT) during pregnancy is a det erm ining fact or t hat cont ribut es t o increased m at ernal- fet al m orbidit y and m ort alit y. I t m ay occur when t here is t hrom bophilia, due t o com pression of t he inferior vena cava, venous st asis or horm onal changes. Obj e ct ive s: To assess pat ient s who are pregnant or have j ust given birt h and who have a DVT condit ion in t he lower lim bs, t o search for possible causes of t hrom bophilia and t o perform a review of t he lit erat ure.
M et hods:Pregnant and puerperal pat ient s were assessed by gynecologist s and obst et ricians when t here was suspicion of DVT, from January 2004 t hrough Novem ber 2006, during which t im e t here were 24,437 childbirt hs at Hospit al e Mat ernidade São Luiz; of t hese, 89% were cesarean, 7.5% were norm al birt hs and 3.5% were forceps deliveries. Of t he t ot al num ber of pat ient s referred wit h a clinical st at us suggest ing DVT, 42 cases were clinically diagnosed as DVT, in pregnant wom en aged bet ween 21- 39 years, confirm ed by venous duplex scan. Right before t he int roduct ion of
ant icoagulant t herapy, sam ples were collect ed t o invest igat e t hrom bophilia, which were repeat ed aft er t he t reat m ent .
Re sult s:Of t he 42 pat ient s wit h DVT, 32 were prim igravid ( t hree t win pregnancies wit h no
diagnost ic of DVT ( no t hrom bophilia) aft er a cesarean sect ion. Of t he 42 pat ient s, 16 ( 38.1% ) had t he cause of t heir DVT det erm ined, wit h a prevalence of het erozygous m ut at ion of fact or V Leiden in six pat ient s ( 14.2% ) , followed by phospholipid syndrom e and ot her causes. Most pat ient s were t reat ed wit h low- m olecular- weight heparin.
Conclusion: DVT during pregnancy, despit e having low frequency, is a m aj or cause of increased m at ernal- fet al m orbidit y. I nvest igat ion of t hrom bophilia should be conduct ed in select ed cases, such as personal or fam ily hist ory of t hrom bot ic phenom ena and/ or t hrom bophilia. Twin pregnancy, cesarean birt h and art ificial insem inat ion were also found as fact ors leading t o DVT.
Keyw ords: Deep venous t hrom bosis, t hrom bosis, pregnancy, ant icoagulant , heparin.
RESUM O
Cont ex t o: A t rom bose venosa profunda ( TVP) na gravidez é fat or det erm inant e no aum ent o da m orbidade e da m ort alidade m at ernofet al. Pode ocorrer na presença de t rom bofilias, por com pressão da veia cava inferior, est ase venosa ou alt erações horm onais.
Obj e t ivos: Analisar pacient es grávidas e no pós- part o im ediat o port adoras de TVP em m em bros inferiores, pesquisar as possíveis causas de t rom bofilia e realizar revisão de lit erat ura.
M ét odos: Foram analisadas gest ant es e puérperas encam inhadas por ginecologist as e obst et ras com quadro clínico suspeit o de TVP, de j aneiro de 2004 a novem bro de 2006, período em que foram realizados 24.437 part os no Hospit al e Mat ernidade São Luiz ( HMSL) , sendo 89% cesarianas, 7,5% part os norm ais e 3,5% fórceps. Do t ot al de pacient es encam inhadas com quadro clínico sugest ivo, foram realizados 42 diagnóst icos clínicos de TVP em gest ant es com idade ent re 21 e 39 anos, confirm ados por duplex scan venoso. I m ediat am ent e ant es da int rodução da t erapia ant icoagulant e, foram colhidos exam es para pesquisa de t rom bofilia, os quais foram repet idos após o período de t rat am ent o.
Re sult a dos:Das 42 pacient es port adoras de TVP, 32 eram prim igest as ( t rês gem elares sem alt erações t rom bofílicas, duas por fecundação in vit ro) , oit o secundigest as e duas t ercigest as. Em quat ro pacient es, a TVP ocorreu no prim eiro t rim est re da gest ação ( 9,5% ) ; em 11, no segundo t rim est re ( 26,2% ) ; em 27, no t erceiro t rim est re ( 64,3% ) . Dos 42 casos de diagnóst ico de TVP, 18 ( 42,8% ) ocorreram nas veias infrapat elares. Houve um caso de t rom boem bolism o pulm onar ( TEP) em pacient e de 37 anos que havia realizado fecundação in vit ro, com gest ação gem elar, e TVP ( ausência de t rom bofilia) diagnost icada após a cesariana. Das 42 pacient es, 16 ( 38,1% ) t iveram a causa da TVP est abelecida, com prevalência de m ut ação het erozigót ica do fat or V de Leiden ( FVL) em seis pacient es ( 14,2% ) , seguida pela síndrom e ant ifosfolípide e out ras. A m aioria das pacient es foi t rat ada com heparina de baixo peso m olecular.
Conclusã o:A TVP na gravidez, apesar de sua baixa freqüência, aum ent a consideravelm ent e a m orbidade m at ernofet al. A pesquisa de t rom bofilia deve ser realizada em casos selecionados, t ais com o ant ecedent es pessoais ou fam iliares de fenôm enos t rom bót icos e/ ou t rom bofilia. A gest ação gem elar, a cesariana e a insem inação art ificial t am bém foram fat ores predisponent es para a ocorrência de TVP.
Pa la vr a s- cha ve:Trom bose venosa profunda, t rom bose, gest ação, gravidez, ant icoagulant e, heparina.
I nt roduct ion
em bolism .1 - 4 High num ber of cesarean deliveries has significant ly cont ribut ed t o increase in incidence of t hrom boem bolic phenom ena. Pulm onary t hrom boem bolism ( PTE) , deep venous t hrom bosis ( DVT) in pregnancy and in t he puerperium are det erm ining fact ors for increase in m at ernal- fet al m orbidit y and m ort alit y. There are report s bet ween 0.5 and t hree cases of DVT for each 1,000 pregnancies. Som e aut hors have est im at ed t hat DVT in pregnant wom en is five t im es m ore frequent t han in nonpregnant wom en in t he sam e age group.
Pregnancy is a st at e of preparat ory hypercoagulabilit y for delivery, by product ion of plasm inogen inhibit ors 1 and 2 t hrough t he placent a, reducing fibrinolyt ic act ivit y and increasing plat elet aggregat ion. There are also reduct ion in prot ein S levels, increase in fact ors I , VI I , VI I I and X and progressive resist ance t o prot ein C act ivit y.2 , 3 Concom it ant ly, com pression of t he inferior vena cava by t he pregnant ut erus cont ribut ed t o venous st asis, t hus favoring t hrom bot ic phenom ena.5
Throm bophilia, described as a t endency t o developm ent of t hrom bosis, can be heredit ary or acquired. I t is polym orphic as t o genet ic condit ion for plat elet s or prot eins of coagulat ion fact ors. When present , it favors t he previously described t hrom bot ic phenom ena in pregnancy.
Hyperhom ocyst einem ia is an exam ple of bot h heredit ary and acquired t hrom bophilia ( defect in hom ocyst eine m et abolism or folat e- deficient diet ) . Bot h cause increase in plasm a hom ocyst eine and higher possibilit y of t hrom bosis.3
DVT in pregnancy and in t he post part um period subst ant ially increases m at ernal- fet al m orbidit y and m ort alit y, placing t wo lives at risk. These fact ors, associat ed wit h our hospit al- m at ernit y experience, m ot ivat ed us t o perform t his research st udy.
This art icle analyzes t he causes of t hrom bosis during pregnancy and im m ediat e post part um period in pat ient s wit h lower lim b DVT at Hospit al e Mat ernidade São Luiz ( HMSL) , in São Paulo, Brazil, from January 2004 t hrough Novem ber 2006, and perform s a lit erat ure review.
M et hods
Fort y- t wo pregnant wom en were analyzed, aged bet ween 21- 39 years, referred by HMSL obst et ricians and gynecologist s t o be assessed by our t eam , wit h clinical suspicion of DVT from January 2004 t hrough Novem ber 2006, when t here was a record of 24,437 deliveries (Table 1) . Diagnosis was based on clinical signs and sym pt om s. Personal and fam ily hist ory of t hrom bophilia and t hrom boses were exhaust ively invest igat ed. Pain, edem a and calf t enderness were present in m ore t han 80% of pat ient s; Hom ans' sign, superficial venous dilat at ion and cyanosis were present at a lower proport ion. Of all referred pat ient s, 42 had clinical diagnosis of DVT confirm ed by venous
I m m ediat ely before int roduct ion of ant icoagulant t herapy and 1 m ont h aft er it s end, t he following exam inat ions were perform ed for invest igat ion of t hrom bophilia: dosage of ant it hrom bin and prot ein C ( funct ional m et hod wit h chrom ogenic subst rat e) , det erm inat ion of prot ein C ( coagulom et ric
m et hod) , fact or V Leiden ( FVL) m ut at ion ( R506Q m ut at ion by PCR- RFLP) in t he fact or V gene, I gG ant icardiolipin ( im m unoenzym at ic) , I gM ant icardiolipin ( im m unoenzym at ic m et hod) , lupus
ant icoagulant ( aut om at ed BCS m et hod) , prot hrom bin m ut at ion ( PCR m et hod t o det ect G20210A m ut at ion of t he prot hrom bin gene) and hom ocyst eine dosage ( high- perform ance liquid
chrom at ography or HPLC m et hod) . I nclusion crit eria for t hrom bophilia were est ablished aft er clinical and ult rasound confirm at ion of DVT, and especially aft er confirm at ion of t hrom bophilia before and aft er t he t reat m ent . Blood count , coagulogram , echocardiogram and D- dim er were also perform ed t o evaluat e t he t reat m ent and com orbid condit ions.
Low- m olecular- weight heparin ( LMWH) was t he first- choice drug, being careful t o cont rol dosage t o avoid levels of act ivat ed part ial t hrom boplast in ( APTT) higher t han 1.5- 2 t im es t he norm al value. Lim it ing fact or for it s use was t he drug's high cost . Not all pat ient s had financial condit ions t o m aint ain LMWH t reat m ent . I n t hese cases, we chose subcut aneous unfract ionat ed heparin ( UFH) , also adj ust ed according t o APTT levels bet ween 1.5- 2 t im es t he norm al level. Plat elet cont rol was m onit ored by coagulogram .
Minim al ant icoagulat ion t im e was 3 m ont hs. I n t he group of pat ient s wit h t hrom bosis in t he first and second pregnancy t rim est ers, it reached t he puerperal period in cases of t hrom bophilia. Treat m ent was suspended 24 hours before delivery and resum ed 6 hours aft er anest hesia. I n suspicion of t hrom bophilia, t reat m ent was suspended 2 m ont hs aft er delivery, when t hrom bophilia result s were confirm ed in 12 cases. Three pat ient s who were init ially considered posit ive for t hrom bophilia during pregnancy did not have laborat ory confirm at ion aft er t he t herapy. Pat ient s wit h t hrom bophilia were t hen referred t o a hem at ologist .
I n cases of great saphenous t hrom bosis, surgical t reat m ent was chosen t hrough aort ic arch ligat ion using local anest hesia, wit h no sedat ion.
Oral ant icoagulat ion was not used in any case, neit her fibrinolyt ic drugs or im plant at ion of inferior vena cava filt er.
Result s
From January 2004 t hrough Novem ber 2006, 24,437 deliveries were perform ed at HMSL and 25,055 birt hs were recorded; of t hese 21,748 were cesarean ( 89% ) , 1,832 were norm al ( 7.5% ) and 857 forceps deliveries ( 3.5% ) (Table 1) . Decision as t o procedure was m ade according t o clinical indicat ion or pat ient 's choice, excluding any int erference by t he HMSL, which recom m ends norm al delivery as t he first opt ion. Of all pregnant wom en, 14,110 were prim iparous ( 57.7% ) . Pat ient s wit h clinical suspicion of DVT were referred, and 42 diagnoses were confirm ed by our vascular surgery t eam . Tot al occurrence of t hrom bosis m ust be higher, since t he HMSL is a privat e hospit al, open t o all specialist s in São Paulo, and ot her DVT have cert ainly been t reat ed by ot her angiologist s. Of t he 42 pat ient s wit h DVT, 32 were prim igravid ( 76% ) , of whom t hree had t win pregnancy wit hout t hrom bophilic changes and t wo had in vit ro fecundat ion, eight were m ot hers at second birt h ( 19% ) and t wo were at t hird birt h ( 5% ) (Table 2) . The pat ient s' age ranged bet ween 21- 39 years. Two were sm okers.
I n four pat ient s, DVT occurred in t he first pregnancy t rim est er ( 9.5% ) ; in 11 in t he second t rim est er ( 26.2% ) ; in 27 in t he t hird t rim est er ( 64.3% ) , including four post- cesarean sect ions (Table 2) . There was one case of PTE on t he first post- cesarean day in a 37- year- old pat ient who had perform ed in vit ro fecundat ion, wit h t win pregnancy ( no t hrom bophilic change) , whose diagnosis of infrapat ellar DVT was perform ed aft er PTE.
deliveries.
I n 16 pat ient s ( 38% ) , DVT et iology was defined (Table 3) ; 12 pat ient s ( 28.5% ) had posit ive result s for t hrom bophilia in pre- and post - coagulat ion exam s; six pat ient s ( 14.3% ) had FVL het erozygot ic m ut at ion; t hree ( 7.1% ) had ant iphospholipid syndrom e ( t wo had syst em ic eryt hem at ous lupus) , ant it hrom bin deficiency, prot ein C deficiency and prot ein S deficiency ( one pat ient each) . Four non-t hrom bophilic wom en had non-t he following facnon-t ors as denon-t erm ined cause: polycynon-t hem ia vera ( one case) ; long plane t rip ( one case) ; and great saphenous t hrom bophlebit is in proxim al t hird of t he t high ( t wo cases) . We credit ed t he ot her 26 cases ( 61.9% ) t o alt erat ions t hat are t ypical of pregnancy (Table 3) . Three of t hese pat ient s had exam inat ions suggest ive of t hrom bophilia in DVT diagnosis, but we had no post - t reat m ent confirm at ion, t herefore t hese pat ient s were excluded from t he t hrom bophilia group.
Discussion
Many changes occur in pregnancy and cont ribut e t o hypercoagulabilit y.6 Pregnancy can be
considered a form of dissem inat ed int ravascular coagulat ion due t o reduced fibrinolyt ic act ivit y and increased plat elet aggregat ion. During pregnancy t here are alt erat ions such as reduced prot ein S and ant it hrom bin, resist ance t o prot ein C act ivit y, elevat ion of fact ors I ( fibrinogen) , VI I , VI I I
( hem ophilic) , X and von Willebrand.3 These changes of a t hrom bogenic nat ure are preparat ory resources for delivery, reducing risks of bleeding for t he m ot her. Twent y- six pat ient s ( 61.9% ) , out of a t ot al of 42, had DVT due t o changes exclusive of pregnancy (Table 2) , whereas in ot her 16 wom en t hey were at t ribut ed t o t hrom bophilias, polycyt hem ia vera, great saphenous vein t hrom bophlebit is and long t rips. I n addit ion t o t he above m ent ioned, t here m ay be ot her causes of acquired
t hrom bophilias, such as nephrot ic syndrom e, hepat ic diseases, surgeries ( including cesarean sect ions) , oral cont racept ive, est rogens and progest agens used in art ificial insem inat ions.
During t he first t rim est er of pregnancy, t here is increased venous pressure due t o hyperflow in t he hypogast ric and com m on iliac art eries, result ing from relaxat ion of vessel sm oot h m uscles and opening of art eriovenous anast om oses due t o progest ogen act ivit y. During t he second and t hird t rim est ers, in addit ion t o t hese fact ors, t here is inferior vena cava com pression due t o pregnant ut erus, result ing in reduced venous flow.5 I n t he present st udy, we observed t hat DVT occurred m ore frequent ly in t he t hird t rim est er of pregnancy, in 27 cases ( 64.3% ) , probably due t o equivalence of procoagulat ing fact ors and st asis, followed by t he second and t hird t rim est ers, respect ively. Four pat ient s ( 9.5% ) had DVT in t he im m ediat e post- cesarean period. This is m ainly due t o pelvic t raum a of fem oral, iliac and t ribut ary veins, in addit ion t o an equally t hrom bogenic surgical procedure, according t o Virchow's t riad, described in 1860.
t im es higher aft er cesarean sect ions when com pared t o norm al and forceps deliveries. Risk of
t hrom bosis in pregnancy is considered higher during t he t hird t rim est er of pregnancy, and especially in t he puerperium ( up t o 6 weeks aft er delivery) ; however, prospect ive st udies using obj ect ive diagnost ic t est s did not show any difference bet ween frequency of DVT and pregnancy t rim est ers.2 Sim ilarly, recent analyses have shown t hat DVT in pregnancy is at least as com m on as post part um DVT.9
I ncidence of DVT is sim ilar in m en and wom en, and it is m ore frequent in Caucasian wom en when com pared t o Asians.1 0 I t is not com m on t o occur before 20 years of age, but aft er 40 years incidence doubles at each decade. Since m at ernit y occurs at increasingly lat er ages and due t o increase in num ber of in vit ro insem inat ions and cesarean sect ions, t here will be a higher t endency of DVT1 1 in pregnancies. I t is also im port ant t o observe t hat m ore t han half of PTE episodes result from DVT, and 75% of t hese occur in t he first episode.1 2 Risk fact ors for a first DVT event m ay usually be present for recurrence. A det ailed anam nesis, especially in pat ient s wit h previous and fam ily hist ory of t hrom boem bolic phenom ena, should lead t o laborat ory invest igat ion in select ed pregnant wom en.
Perform ing duplex scan aft er t he 20t h week m akes it s int erpret at ion m ore difficult , due t o alt erat ion in venous ret urn; t herefore, serial exam inat ions at every 7 days should be perform ed in case of doubt .2 Duplex scan should be t he choice exam inat ion t o invest igat e pregnant pat ient s wit h suspicion of DVT.1 , 6 - 8 D- dim er was not considered, since it can be high during pregnancy, progressively
increasing t hroughout pregnancy and possibly reaching high levels ( up t o 30% ) , which m akes rout ine assessm ent useless.3
I n t he present st udy, t hrom boses occurred m ore frequent ly in t he left lower lim b, 23 ( 54.8% ) vs. 19 ( 45.2% ) in t he right lower lim b. Despit e t hat difference not being considered significant , t he
lit erat ure st at es t hat approxim at ely 80% of cases occur in t he left leg, due t o abnorm al com pression of t he left iliac vein by t he right com m on iliac art ery ( Cocket syndrom e) .2 I nfrapat ellar locat ion in our populat ion was m ore frequent , in agreem ent wit h t he lit erat ure.
As t o num ber of pregnancies and DVT, we observed a higher frequency in prim igravid wom en ( 76% ) , followed by m ot hers at second birt h ( 19% ) and at t hird birt h ( 5% ) . Perhaps t hese num bers reflect t he great m aj orit y of prim igravid wom en adm it t ed t o our hospit al: 14,110 ( 57.7% ) out of 24,437 deliveries.
We observed t hat in t hree prim igravid pat ient s wit h t win pregnancy DVT possibly occurred due t o higher com pression of t he inferior vena cava as a result of large pregnant ut erus.
Two part urient wom en had in vit ro fert ilizat ion. This t ype of fecundat ion favors t hrom bogenic phenom ena, due t o horm one t herapy wit h est rogen and progest erone in high doses. Korint oya report ed t hat in vit ro fert ilizat ion m ay cause ovarian hyperst im ulat ion syndrom e and favor t hrom bosis in lit t le frequent locat ions, such as subclavian and j ugular art eries.1 3
As t o t hrom bophilias, we observed t hat t here was a higher prevalence of FVL m ut at ion ( six cases) and ant iphospholipid syndrom e ( t hree cases) , followed by ant it hrom bin, prot ein S and C deficiency ( one case each) .
FVL m ut at ion, which was t he m ost present cause in our populat ion, is m ore frequent in individuals from Nort hern Europe ( 3- 8% ) , being rare in Asians and Africans. I n t he USA, prevalence is 4- 6% .3 Langan et al. report ed t hat FVL m ut at ion predisposes t o pre- eclam psia due t o m arked fibrin deposit ion, result ing in endot helial lesion t hat m ay cause vasospasm , plat elet act ivat ion and coagulat ion.1 4 , 1 5 Sim ilarly, m ut at ion delays int raut erine fet al growt h, can be t he cause of recurrent abort ions, favors fet al deat h and significant ly raises incidence of t hrom bosis during pregnancy.1 0 , 1 4 , 1 5 Analogously, it is responsible for recurrent venous t hrom boses. Becker report ed t hat individuals can be het erozygot e or hom ozygot e for FVL m ut at ion; t hrom bosis occurs m ore frequent ly in
hom ozygot es. I n het erozygot es, t he first episode of t hrom bosis usually occurs when t here are im posed risk fact ors, such as surgery, oral cont racept ives or pregnancy.
Three pat ient s had t hrom bosis wit h posit ive ant iphospholipid ant ibody; t wo had eryt hem at ous lupus. Presence of ant iphospholipid ant ibodies in pregnant wom en, besides causing DVT, increases
incidence of abort ions in t he second t rim est er ( due t o DVT) , favors pre- eclam psia, delays int raut erine fet al growt h and m ay cause fet al deat h.1 6
Di St efano described t hat prot ein C, prot ein S and ant it hrom bin deficiencies reduce placent al perfusion1 5 ( in t he present st udy, we observed one pat ient in each group) . When present , prot hrom bin m ut at ion is also a t riggering fact or of DVT.
McCool published a m ult i- cent ered st udy involving superficial t hrom bophlebit is ( STP) in pregnant wom en. He found an average of 0.68 STP/ 1,000 deliveries and concluded t hat t hrom bophilia can be t he lowest STP et iology in pregnancy. More com prehensive st udies are necessary t o confirm t hat hypot hesis.1 7 , 1 8
One pat ient wit h polycyt hem ia vera had DVT in our populat ion. Robinson1 9 report ed only 20 cases of polycyt hem ia vera associat ed wit h pregnancy, which m ay be relat ed t o prem at ure birt hs and fet al deat h. For t hat reason, careful at t ent ion should be given t o hem at ocrit .1 9 , 2 0
One pat ient had DVT aft er a long plane t rip. Kingm an2 1 published an art icle suggest ing t hat pregnant wom en should t ravel in t he second t rim est er, which offers lower risk and m ore com fort ( som e airline com panies do not allow pregnant wom en at m ore t han 36 weeks t o board t heir airplanes) . Robin also warned t hat pregnant wom en are not always prepared t o t ake long t rips.2 1 During t hat period,
t ravelers, especially pregnant wom en, should adopt prophylact ic m easure for t hrom bosis, such as walking, perform ing foot and leg flexion and ext ension and wearing ant it hrom bot ic st ockings; in case t here is personal hist ory of t hrom bophilia and/ or t hrom bosis, LMWH can be indicat ed.2 1 , 2 2
One pat ient subm it t ed t o cesarean sect ion, t win pregnancy, in vit rofert ilizat ion had PTE in t he im m ediat e post operat ive period when ret rospect ive DVT diagnosis was perform ed.
Ant icoagulant t herapy aim s at prevent ing PTE, avoiding harm t o t he fet us ( hem orrhage,
t erat ogenesis, m alignancy and genet ic m ut at ions) relieving acut e and uncom fort able sym pt om s in wom en, m inim izing post phlebit ic sequelae of t hat disease,3 besides prevent ing t he t hrom bophilia com plicat ions m ent ioned above.8 Thus, t reat m ent onset should be as early as possible. LMWH and convent ional heparin do not cross placent al barrier, opposed t o warfarin, which has risk of fet al m alform at ion, especially bet ween t he sixt h and 12t h gest at ional week, besides providing m ore hem orrhagic com plicat ions. Therefore, warfarin should be avoided during t he gest at ional period.3 , 6 , 2 3 Fibrinolyt ics are included in t he sam e cat egory.2 4
LMWH t han in UFH. Som e aut hors recom m end cont rol of blood heparin ( by ant i- fact or Xa act ivit y, especially in t he last t rim est er) . Som e pat ient s had no financial condit ions t o m aint ain LMWH t reat m ent . I n such cases, we chose t o use UFH, adj ust ed wit h APTT. I n bot h t reat m ent s, we also perform ed plat elet count , since t here m ay be low plat elet count associat ed wit h heparin use. Two pat ient s who had sm all m et rorrhagia used UFH; drug suspension or use of prot am ine were not necessary. They rem ained under clinical observat ion and had t heir hem at ocrit and hem oglobin levels m onit ored.
I n cases of ant iphospholipid syndrom e, LMWH associat ed wit h aspirin seem s t o have a significant ly bet t er result .3
Fokkin2 8 published a st udy on 16 cases of t em porary vena cava filt er im plant at ion in pregnant wom en in t he t hird t rim est er of pregnancy. Ot her aut hors have report ed t hat ant icoagulat ion wit h perm anent or t em porary vena cava filt er insert ion did not have post part um com plicat ions. These aut hors support t he t hesis t hat t he filt er can be an efficient prophylact ic alt ernat ive or in t he t reat m ent of pregnancy wit h high risk of DVT in pat ient s in whom t here is cont raindicat ion for ant icoagulat ion.9 We did not use t hat procedure in any case.
Conclusions
- DVT in pregnancy has low occurrence, but it considerably increases m at ernal- fet al m orbidit y, bringing high risk t o t he pregnancy.
- Prim igravid pat ient s, t win pregnancies, cesarean sect ions and puerperium had higher risks for DVT.
- I n vit ro fert ilizat ion has m ore suscept ibilit y t o DVT, due t o high doses of est rogen and progest erone required t o t hat m odel of pregnancy.
- Clinical DVT invest igat ion, using anam nesis, personal and fam ily hist ory of t hrom bophilia, clinical exam inat ion, being careful for age over 35 years and obesit y, should be part of prenat al prot ocol and deserves relevant at t ent ion for risk of t hrom bosis in pregnancy. I n suspect ed cases, laborat ory exam inat ion is prudent .
- LMWH t reat m ent seem s t o be t he m ost indicat ed, since it had lower m at ernal- fet al com plicat ions; however, cost can be a lim it ing fact or.
- Oral ant icoagulant s and fibrinolyt ics should not be used during pregnancy.
- Prophylact ic doses of heparin are recom m ended during and aft er pregnancy for wom en who are confirm edly t hrom bophilic and wit h previous hist ory of venous t hrom boem bolism .
References
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Correspondence:
Jorge A. Kalil
Rua Itapeva, 240/1605, Bela Vista CEP 01332-000 – S†o Paulo, SP, Brazil Tel.: (11) 3253.3034, (11) 8383.3300 Email: [email protected]
