Acquired Haemophilia

Publish in



Please download to get full document.

View again

of 4
All materials on our website are shared by users. If you have any questions about copyright issues, please report us to resolve them. We are always happy to assist you.
Arch Iranian Med 2007; 10 (1): 107 – 110 Case Report Acquired Hemophilia as a Cause of Primary Postpartum Hemorrhage Sedigheh Borna MD *, Sedigheh Hantoushzadeh MD* ã A 32-year-old primigravid woman developed acquired factor VIII inhibitor after delivery. She presented with postpartum hemorrhage and large hematoma in episiotomy site. Laboratory examinations showed markedly prolonged activated partial thromboplastin time, low levels of factor VIII (8%), and factor VIII inhibitor (2 Bethesda un
  Arch Iranian Med 2007; 10 (1): 107 – 110  Archives of Iranian Medicine , Volume 10, Number 1, January 2007107   Acquired Hemophilia as a Cause of Primary PostpartumHemorrhage Sedigheh Borna MD ã *, Sedigheh Hantoushzadeh MD* A 32-year-old primigravid woman developed acquired factor VIII inhibitor after delivery. Shepresented with postpartum hemorrhage and large hematoma in episiotomy site. Laboratoryexaminations showed markedly prolonged activated partial thromboplastin time, low levels offactor VIII (8%), and factor VIII inhibitor (2 Bethesda units). The bleeding was controlledsuccessfully using combined treatment with factor VIII, intravenous immunoglobulin, steroids, andrecombinant factor VIIa. Six months after delivery, factor VIII inhibitor was not present and factorVIII concentration increased to normal range.Acquired hemophilia is a life-threatening disorder. Precise screening of coagulation factors isessential for diagnosis of persisting postpartum hemorrhage. Archives of Iranian Medicine, Volume 10, Number 1, 2007: 107 – 110. Keywords: Acquired hemophilia A   ● factor VIII inhibitor  ●   postpartum hemorrhage Introduction cquired hemophilia A is an uncommonhemorrhagic disorder caused byspontaneous occurrence of autoantibodies directed against the factor VIII.These inhibitors that develop in nonhemophilicpatients are associated with various underlyingconditions such as pregnancy, lymphoproliferativeor myeloproliferative disorders, solid tumors,autoimmune diseases, and allergic reactions tomedications (penicillin, chloramphenicol, andphenytoin). 1, 2  Acquired hemophilia A is rare. Its incidence isabout 1 per 5 million individuals per year. About14% of cases with acquired hemophilia can beidentified in the postpartum period. Such patientsusually show postpartum hemorrhage (PPH) oruncontrolled bleeding after surgical interventions.The clinical picture is often severe and life-threatening with a death rate between 10 – 22%depending on case series. 3 Severe, prompt, andaccurate diagnosis is necessary in order to provideadequate treatment. Case Report A 32-year-old primigravid a woman, with nosignificant medical history delivered a 3,500 gfemale neonate at 40 th gestational week in a localhospital, 12 days prior to admission.The pregnancy was uncomplicated until 2 daysafter delivery. Two days after discharge, shedeveloped intermittent vaginal bleeding, withpassage of a large clot along with large hematomain the episiotomy site. A dilatation and curettagewas performed for the presumed retained productsof conception. The large hematoma was evacuatedand the site was sutured. A few days later, thepatient continued to have heavy spotting andpassage of clots, along with large hematoma in thevulva. She received methylergonovine plusoxytocin and dilatation and curettage wasperformed again. The patient required multipletransfusions for persistent blood loss. Because of the uncontrollable bleeding and prolonged partialthromboplastin time (PTT) (89 second), the patientwas referred to our academic hospital 12 days afterdelivery.On admission, she was severely anemic and had Case Report A Authors’ affiliation:   * Department of Obstetrics and Gynecology,Tehran University of Medical Sciences, Tehran, Iran. ãCorresponding author and reprints: Sedigheh Borna MD, 2ndFloor, Vali-e-Asr Hospital, Imam Khomeini Hospital Complex,Keshavarz Blvd., Tehran 14194, Iran. Tel: +98-216-6937766,Fax: +98-218-8718062, E-mail: for publication: 19 April 2006    Acquired hemophilia as a cause of primary PPH  Archives of Iranian Medicine , Volume 10, Number 1, January 2007108 intermittent vaginal bleeding. Vaginalultrasonography of the pelvis did not reveal anyabnormal findings in the uterus and pelvis. Thelaboratory results showed hemoglobin = 5.6 g/dL,and an activated PTT = 89 seconds. Otherlaboratory tests, including prothrombin time (PT),platelet count, and D-dimers, were within normallimits. The results of the other tests such asrheumatoid factor, antinuclear antibody,anticardiolipin IgG, and HIV were all normal ornegative.Further work-up revealed low levels of factorVIII (8%). A factor inhibitor screen wasperformed, and the result was positive, with a titerof 2 Bethesda units (BU). Laboratory data aresummarized in Table 1.The absence of familial and personal bleedinghistory plus normal vaginal ultrasonography of pelvis and laboratory tests, accompanied by thefact that the PTT was not corrected following theinfusion of normal plasma led us to presume that acoagulation inhibitor was involved. Afterconsultation with senior hematologists, we decidedto transfuse packed red blood cell and humanfactor VIII. Intravenous immune globulin (IVIG)40 g/day for 2 days and tranexamic acid l g every12 hours were used too. Immune suppression wasstarted at the same time with prednisone50 mg per day.The patient received uterotonic drugs such asoxytocin and ergot alkaloids. We also began acourse of intravenous antibiotics for possibleendometritis and wound infections.After 3 days, the patient continued to havevaginal bleeding and passage of clots. Thelaboratory results showed a prolonged activatedPTT (77 second).Recombinant factor VIIa (Novo seven) wascommenced as the final attempt to control thebleeding. An intravenous bolus injection of 90µg/kg Novo seven was started, followed by 60µg/kg after 2 hours. The same dose was thenadministered every 4 hours for 48 hours, thenevery 8 hours for 2 days more. Using this methodof treatment, the vaginal bleeding was quicklycontrolled and hemoglobin levels stabilized. Novoseven and factor VIII were discontinued after 8days (Table 2). Ten days after admission, thepatient was discharged from the hospital in goodclinical condition. Prednisone was continued for 4weeks and then gradually tapered. Three monthsafter delivery, factor VIII inhibitor was 1 BU andfactor VIII concentration was 50% (normal range:60 – 120%). Six months after delivery, factor VIIIinhibitor was not present and factor VIIIconcentration had increased to normal range(Table 3). Discussion PPH is a major cause of maternal mortality andmorbidity worldwide. The most common cause of PPH is uterine atony. 3 Other causes includeretained placental tissues, abnormal adhesion of the placenta, lower genital laceration, uterinerupture, and coagulopathy. Our patient hadacquired hemophilia A, which was a result of factor VIII inhibitor production. The patient’sdisease was diagnosed by a coagulation profile,which showed isolated elevation of the PTT. Othercoagulation parameters were normal. The next testdone was a check of individual factor levels, whichrevealed low factor VIII activity. The factorinhibitor screen showed a titer of 2 BU.   Michielset al 2 have reviewed 27 patients with postpartumfactor VIII inhibitors; these patients had over 100bleeding episodes and only one patient hadsignificant bleeding during pregnancy. Six patients Table 2. Treatment modalities. Agents Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Human factor VIII 50 U/kgdaily50 U/kgdaily50 U/kgdaily50 U/kgdaily50 U/kgdaily50 U/kgdaily50 U/kgdaily50 U/kgdailyIVIG 40 g 40 g — — — — — —Tranexamic acid 1 g/BID 1 g/BID 1 g/BID 1 g/BID 1 g/BID 1 g/BID 1 g/BID 1 g/BIDPrednisone 50 mg 50 mg 50 mg 50 mg 50 mg 50 mg 50 mg 50 mgrFVIIa (Novo seven) 60 µg/kgQID60 µg/kgQID60 µg/kgQID— — — — — rFVIIa = recombinant activated factor VII. Table 1. Laboratory values at admission. Hemoglobin 5.6 g/dLHematocrit 15%Platelet 160×10³/µLPTT 89 secondsPT 12 secondsFibrinogen 358 mg/dLD-dimers 0.2 – 0.4 µg/mLFibrin split products < 5 mg/LFactor VIII inhibitor 2 Bethesda unitsFactor VIII 8%    S. Borna, S. Hantoushzadeh  Archives of Iranian Medicine , Volume 10, Number 1, January 2007109 had significant PPH and in five of these patientsthe PPH lasted for several weeks. Two of thesepatients had undergone laparotomy withhysterectomy before the coagulation defect wasdetected. Mortality occurred in three patients; onepatient died shortly after delivery due touncontrollable bleeding and two other patients dieddue to respiratory obstruction following laryngealhemorrhage and retroperitoneal bleeding,respectively. In a more recent survey, 14 additionalnew cases of postpartum acquired hemophilia havebeen analyzed. These patients had a total of 80bleeding episodes, 34 of which were severe andfive were life-threatening. One patient had severePPH requiring hysterectomy . 3  When medical treatments and conservativesurgical procedures fail to control the bleeding,hysterectomy is usually needed. 3, 4 Emergencyhysterectomy is associated with significant bloodloss, and more postoperative complications. Ourpresented case showed that early recognition of aprolonged activated PTT in a bleeding patient isessential for the diagnosis and initiation of adequate treatment. Our case also showed thataccurate diagnosis and adequate treatment couldsuccessfully control life-threatening PPH inwomen who had acquired hemophilia A andemergency hysterectomy was not needed.Patients who develop hemophilia A duringpostpartum period usually present within 1 to 4weeks after delivery. Acquired postpartumhemophilia usually affects the first pregnancy andfuture pregnancies are rarely affected. 3, 4 Theprognosis of acquired hemophilia A depends onthe underlying disorder and the inhibitor titer.Postpartum and idiopathic forms as well as thosewith low inhibitor titer, have more favorableprognosis. 4  The antenatal transplacental transmission of factor VIII has been reported in a case of severeneonate intracranial hemorrhage, 4 but in our casethe neonatal had normal factor VIII levels andthere were no neonatal sequel.Management of this disease should be aimed atstopping the hemorrhage, raising endogenousfactor VIII levels, and reducing the inhibitorlevels. 5, 6 Treatment consists of blood products toreplace the blood loss, coagulation factors, andimmunosuppressants.Human factor VIII concentrate may seem alogical choice for treatment, but it can bedangerous in patients whose immune systemresponds to the infusion of factor VIII byincreasing the antibody levels (high responders).An animal-derived product, porcine factor VIII,has been used to maintain the patients’ clottingability while other treatments are used to stopantibody production. Before administering porcinefactor VIII, it has to be determined that thepatient’s antibody does not cross-react with theanimal-derived factor VIII. This treatment usuallyworks best in patients who have antibody titerslower than 50 BU.Prothrombin complex concentrates (e.g.,Konyne, Autoplex T) are available now. These area combination of clotting factors that containactivated forms of factors X and VII, which bypassthe inhibited intrinsic arm of the cascade. Becausethe patients receive activated coagulating factors,there is a risk of converting the situation to athrombotic state. So, the patients must bemonitored for signs of disseminated intravascularcoagulation or deep venous thrombosis.Another available treatment is a recombinantform of factor VIIa (Novo seven). It reacts withtissue factor and activates factor X, stimulating thecommon coagulation cascade and bypassing theinhibited intrinsic arm. 7, 8  Steroids and in most cases cytotoxicchemotherapy are given in the same way they areused for the treatment of other autoimmune-mediated disorders. In addition, IVIGs have beenused with some success but the exact mechanismof action is not clear. However, it is thought thatanti-idiotypic antibodies are present in pooledhuman immunoglobulin that neutralize theacquired inhibitor. 1 Plasmapheresis and plasmaexchange measures are not useful in the treatmentof this disorder. 9 Most patients receive acombination of these treatments. 9  As recombinant factor VIIa was notimmediately available, and our case had life-threatening bleeding, she was initially treated withblood products, IVIG, high dose of factor VIII, andprednisone, but bleeding was not controlled.Finally, recombinant factor VIIa (Novo seven) wasprescribed, which was effective in controlling the Table 3. Laboratory values after treatment. PTT after 3 days 77 secondsPTT after 8 days 41 secondsFactor VIII inhibitor after 3 months 1 BUFactor VIII inhibitor after 6 months NegativeFactor VIII after 3 months 50%Factor VIII after 6 months 90% BU = Bethesda unit.  Acquired hemophilia as a cause of primary PPH  Archives of Iranian Medicine , Volume 10, Number 1, January 2007110 bleeding. In our reported case, the bleeding wassuccessfully controlled with a combination of thesetreatments. Recombinant factor VIIa is an effectivetreatment in postpartum acquired hemophilia A.This case highlights the importance of hematologicinvestigations in persisting PPH. References 1   Boudo F. Acquired factor VIII inhibitors in pregnancy:data from the Italian Hemophilia Register relevant toclinical practice.  Int J Obstet Gynecol . 2003; 110:  311 – 314. 2   Michiels JJ, Bosch LJ, van der Plas PM, Abels J. FactorVIII inhibitor postpartum. Scand J Haematol. 1978; 20:  97 – 107. 3   Solymoss S. Postpartum acquired factor VIII inhibitors:results of a survey.  Am J Hematol. 1998; 59: 1 – 4. 4   Howland EJ, Palmer J, Lumley M, Keay SD. Acquiredfactor VIII inhibitors as a cause of primary postpartumhemorrhage.  Eur J Obstet Gynecol . 2002; 103: 97 – 98. 5   Wiestner A, Cho HJ, Asch AS, Michelis MA,Zeller JA, Peerschke EI, et al. Rituximab in thetreatment of acquired factor VIII inhibitors.  Blood  . 2002; 100: 3426 – 3428. 6   Schaffer LG, Philips MD. Successful treatment of acquired hemophilia with oral immunosuppressivetherapy.  Ann Intern Med  . 1997; 127: 206 – 209. 7   Michiels JJ, Hamulyak K, Nieuwenhuis HK, Novakova I,van Vliet HH. Acquired haemophilia A in womenpostpartum: management of bleeding episodes andnatural history of the factor VIII inhibitor.  Eur J  Haematol . 1997; 59: 105 – 109. 8   Michiels JJ. Acquired hemophilia A in womenpostpartum: clinical manifestations, diagnosis, andtreatment. Clin Appl Thromb Hemost  . 2000; 6: 82 – 86. 9   Hauser I, Schneider B, Lechner K. Postpartum factor VIIIinhibitors. A review of the literature with specialreference to the value of steroid and immunosuppressivetreatment. Thromb Haemost  . 1995; 73: 1 – 5.
Related Search
Related Documents
Acquired Immunity
Sep 25, 2017

Acquired Immunity

View more...
We Need Your Support
Thank you for visiting our website and your interest in our free products and services. We are nonprofit website to share and download documents. To the running of this website, we need your help to support us.

Thanks to everyone for your continued support.

No, Thanks