REGISTRO DOI: 10.5281/zenodo.8322920
Antônio Aurélio de Paiva Fagundes Júnior1, Dennys Augusto de Novais Monteiro2, Lídia Tocchio Melo Monteiro2, Ana Paula Lopes da Silva3, Ester Moraes Dias3, Rafael Passos de Melo4, Laudirene Ramos do nascimento5, Virgília Borel Fumian Gomes5, Igor de Souza Andrade5, Ronald Torres de Olinda4, 6
ABSTRACT
Acquired hemophilia is a rare autoimmune disease caused by depletion of coagulation factor VIII. Its incidence is higher in the elderly, there is no predominance by sex, except in women of childbearing age where there is a higher prevalence of cases. It can develop associated with Systemic Lupus Erythematosus, rheumatoid arthritis, lymphoproliferative diseases, mostly are of idiopathic causes. The goal of treatment is to eliminate the inhibitors through pulse therapy with corticosteroids and treat bleeding with the use of bypass agents.
Keywords: acquired hemophilia, antibodies, Factor VIII, hemorrhage, treatment, case report.
INTRODUCTION
Acquired hemophilia A (AH) is a rare phenomenon caused by the development of neutralizing autoantibodies of Coagulation Factor VIII (factor 8[F8]), different from hemophilia B that affects Factor IX (factor 8[F8]), and evolves with an important hemorrhagic disorder1. It is mostly idiopathic, or due to autoimmune disease, lymphoproliferative disease and also not postpartum2.
Its incidence is 1-4 / million / year with an average presentation between 75-80 years of age3. However, there is a small peak in women between the ages of 20 and 40 years when they preponderate reports in pregnant women3. This disease usually leads to hemorrhage from graves, especially in soft tissues, muscles, mucous membranes, gastrointestinal and intracerebral hemorrhages that are rare but fatal1. Subcutaneous bleeding is the most common (> 80%), followed by muscle bleeding (> 40%); gastrointestinal (> 20%); genitourinary, retroperitoneal and others (<10%) 4.
A therapeutic strategy in patients with AH and control and prevent bleeding (if present or significant) and eradicate inhibitors of Factor VIII4. Immunosuppression with high doses of corticosteroids eliminates autoantibodies and bleeding can be controlled using ignoring agents, such as recombinant Factor VII [rFVIIa: NovoSeven®; Novo Nordisk A / S, Bagsvaerd, Denmark] and the Activated Prothrombin Complex Concentrate [CCPa: Feiba®; Baxter Immuno AG, Vienna, Austria] 5.
We report an experience with a new session admitted to the Emergency Care Unit with pruritus and joint pain. It evolved with extensive hematomas in regions of blood collection being transferred to the Intensive Care Unit (ICU) of the hospital itself, continuing the diagnostic investigation of AH with consequent treatment adequate.
CASE REPORT
A 22-year-old female patient with complaints of pruritus dispersed throughout the body and joint pain. It reports insect bite in the gluteal region for 3 (three) days.
At his admission he had pruritus, hyperemia, edema and pains in right wrist joints; left knee and ankles, with fever and difficulty walking. History of friends using penicillin G benzathine. Laboratory tests indicated normal hemoglobins, platelets and HSV within the reference values, discrete leukocytosis (12,030 / mm3) at the expense of lymphocytes, C-reactive protein of 3.5mg / dL (reference value up to 0.3mg / dL), lactic dehydrogenase (219U/L), normal TSH and free T4. ASLO within normality (168 IU / mL).
Patient maintained pain in joints, being requested Zika virus antibody IgM and IgG and antibody anti chikungunya IgM and IgG, negative. Ecodoppler of lower limbs did not show thrombi. Requested opinion of rheumatology and rheumatologic markers, have been denied for the suspicion of rheumatic fever or rheumatoid arthritis. Patient evolved with moderate bleeding at peripheral venous access sites in jugular vein and upper limbs, central venous access of jugular vein. Hematoma in jugular region with tracheal compression visualized by chest CT. Hemoglobin fall from 8.4 g/dL to 5.9 g/dL, contraindicating invasive procedures and ICU transfer request.
The Inhibitor of Factor VIII, with a value of 8.5 UB (Reference value: less than 5 UB). Thus, closed diagnosis of Acquired Hemophilia. Initiated administration of Feiba and pulse therapy with methylprednisolone. After 8 days, a permanent communication with stable picture.
Table 1 – Laboratory analyzes requested in the first 96 hours of evolution of the case.
| 30/08 | 31/08 | 01/09 | 02/09 | 03/09 | |
| Hgb (g/dL) | 14,2 | 12,8 | 11,6 | 10,0 | 8,4 |
| HCT (%) | 40,7 | 37,4 | 33,4 | 29,3 | 25,0 |
| WBC (mm3) | 12030 | 11380 | 17920 | 14680 | |
| Platelets (103/mm3) | 241 | 253 | 294 | 253 | |
| CRP (mg/dL) | 3,5 | 7,9 | 3,5 | 1,5 | 1,0 |
| TAP (seg) | 11,6 | 12,0 | 11,6 | ||
| INR | 1,06 | 1,06 | |||
| TSH (microU/mL) | 5,93 | ||||
| T4 (ng/dL) | 0,76 | ||||
| BUN (mg/dL) | 29 | 20 | 19 | 23 | 17 |
| Cr (mg/dL) | 0,89 | 1,00 | 0,83 | 0,15 | 0,71 |
| ASLO (UI/mL) | 168 | ||||
| Latex FReumatoide | NR | ||||
| FAN | NR | ||||
| Compl C3 | NR | ||||
| Compl C4 | NR | ||||
| P-ANCA | NR | ||||
| C-ANCA | NR | ||||
| AntiChikung IgG/M | NR | ||||
| ZikaG | NR | ||||
| ZikaM | NR | ||||
| DEN IgG/M | NR |
Table 2 – Temporal evolution of the laboratory analyzes requested 24 hours before ICU stay until the hospital discharge event.
| 04/09 | 05/09 | 06/09 | 07/09 | 08/09 | 09/09 | 10/09 | 11/09 | 12/09 | |
| Hgb (g/dL) | 5,9 | 8,2 | 8,1 | 7,9 | 7,9 | 9,0 | 9,7 | 9,8 | 9,7 |
| HCT (%) | 21,9 | 20,1 | 22,6 | 22,1 | 22,5 | 24,9 | 27,9 | 33,1 | 27,6 |
| WBC (mm3) | 16420 | 14480 | 14310 | 18510 | 15300 | 15180 | 16680 | 14630 | |
| Platelets (103/mm3) | 282 | 237 | 228 | 238 | 197 | 199 | 284 | 327 | |
| CRP (mg/dL) | 0,60 | 0,60 | 1,2 | 1,6 | 0,9 | 2,6 | 6,2 | 3,5 | |
| PRO-BNP (pg/mL) | 195,4 | ||||||||
| TAP (seg) | 10,0 | 8,7 | 10,0 | 11,1 | 11,1 | 11,9 | 10,5 | 12,1 | |
| INR | 1,01 | 1,00 | 0,92 | 1,02 | 1,02 | 1,00 | 0,96 | ||
| TTPA (seg) | 67,9 | 66,5 | 45,4 | 55,2 | 43,9 | 45,1 | 45,4 | ||
| Fibrinogen (mg/dL) | 213,8 | 370,3 | 251,7 | 184,1 | |||||
| pH | 7,410 | 7,402 | 7,411 | 7,399 | 7,430 | 7,406 | 7,405 | 7,359 | |
| pCO2 (mmHg) | 44,9 | 41,8 | 37,4 | 35,2 | 37,0 | 39,5 | 37,6 | 42,3 | |
| HCO3 (mmol/L) | 27,8 | 25,4 | 23,2 | 21,3 | 24,0 | 24,3 | 22,8 | 23,3 | |
| BUN (mg/dL) | 31 | 23 | 47 | 33 | 43 | 26 | 25 | 27 | |
| Cr (mg/dL) | 0,71 | 0,86 | 0,92 | 0,85 | 0,79 | 0,68 | 0,60 | 0,78 | |
| ASLO (UI/mL) | 121 | ||||||||
| FAN | NR | ||||||||
| Lupus Anticoagulant | NR | ||||||||
| Factor VIII (%)* | 0,3 | ||||||||
| Inib Fator VIII (UB)** | 8,5 |
* Reference value: 70 to 150%
** Negative: 0 Bethesda Units; Low inhibitor titre: <5UB; High inhibitor titre> 5UB.
DISCUSSION
We describe the case of a patient diagnosed with HAA. Acquired hemophilia A is a rare autoimmune disease that inhibits coagulation Factor VIII. Treatment consists of eliminating inhibitors and controlling bleeding.
Young patient, admitted to the emergency room with complaints of pruritus diffusely through the body, and pain in joints. It evolved with hematomas in regions of peripheral access and central venous access. She was admitted to the Intensive Care Unit with a drop in hemoglobin levels. If it was discussed together with hematology, closing the diagnosis.
Initially, due to diffuse pruritus and joint pain, the advent of the arbovirus hypothesis was undertaken and diagnostic tests for Dengue, Zika virus and Chikungunya fever were requested. Hypothesis discarded after negative screening. In addition, autoimmune rheumatologic diseases were raised, requiring screening for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). HAA cases can occur associated with RA and SLE, another time is idiopathic origin6.
The suspicion of HAA should be raised in elderly patients and postpartum women with recent onset of abnormal bleeding4. The diagnosis is confirmed by an extended APT, TAP in its normal range, presence of factor VIII inhibitor and negative lupus anticoagulant4.
Treatment is focused on containing more bleeding, eradicating the inhibitor and treating a underlying disease when this is a cause6. Anticoagulants and antiplatelets, arterial punctures, intramuscular injections, invasive procedures and surgeries should be postponed until eradication of inhibitors and recovery of Factor VIII levels6.
The hemostatic agent considered ideal and capable of being monitored, effective and with low potential for adverse effects, such as thrombotic events7.
Recombinant Factor VII [rFVIIa: NovoSeven®] and Activated Prothrombin Complex Concentrate [CCPa: Feiba®] are examples of two drug data. The rFVII favors a production of fiber through extrinsic coagulation, not requiring a participation of factor VIII. CCPa, on the other hand, uses activated factors, ignoring a factor VIII deficiency6. Both have been shown to be effective in the treatment of HAA8.
Direct replacement of human factor VIII proves to be effective only in patients who are low titers (<5 UB); Desmopressin or DDAVP used in mild haemophilia, von Willebrand, purpura with jute community commands of little utility in HAA; antifibrinolytic agents may be useful as adjunctive therapy, except for renal bleeding due to the risk of clot-induced intra-ureteral obstruction4.
The treatment to eradicate the inhibitor is the use of the immunosuppressive potential of isolated corticosteroids (1mg / kg / day) or in combination with cyclophosphamide at low doses (1-2mg / kg / day) in about 4 weeks8.
Our patient, after admission to the ICU and joint research with haematological clinic to diagnose HAA. It presented negative lupus antibody, extended aPTT, low Factor VIII concentration and presence of its inhibitor.
CONCLUSION
Our experience has been described with a patient disease with a rare manifestation disease, an acquired hemophilia A, which presents in a picture of apparent musculoskeletal disease hospitalized for investigation of rheumatologic and arboviral causes. It evolved with bleeding and bruising of great importance in the puncture regions. With fall without hematocrit, admitted to the ICU and, after laboratory investigation, diagnosed with acquired hemophilia A. Appropriate treatment with eradication of inhibitors through pulse therapy with corticosteroids and infusion of activated prothrombin complex. He was discharged from the ICU with a stable condition.
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1. Hospital Ortopédico e Medicina Especializada – HOME, Brasília-DF
2. Faculdades Integradas do Planalto Central – FACIPLAC, Brasília-DF
3. Faculdade Católica de Brasília – UCB, Brasília-DF
4. Centro Universitário de Brasília – CEUB, Brasília-DF
5. Faculdade Anhanguera de Brasília – FAB, Brasília-DF
6. Universidade de Brasília – UnB, Brasília-DF