Doxycycline-induced acquired haemophilia A

An 80-year-old man with no personal or family history of bleeding, presented to hospital with extensive haematomas and skin bruising after using doxycycline. His basic lab workup was concerning for a coagulopathy with an elevated activated partial thromboplastin time and significant anaemia. Mixing studies and other factor levels were tested that led to the diagnosis of acquired haemophilia A with low factor VIII levels and high factor VIII antibodies. He was started on steroids, but his haemoglobin level continued to drop. Later, during his treatment, he was given multiple therapeutic agents, including cyclophosphamide, rituximab and recombinant factor VII (NovoSeven-R). Gradually factor VIII levels increased and haemoglobin stabilised. The hospital course was complicated by COVID-19 pneumonia leading to acute respiratory distress syndrome; the patient eventually expired due to respiratory failure.

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Acute Respiratory Distress Syndrome and Feculent Airway Casts due to Severe Constipation

10.22541/au.162458123.33418948/v1 ◽

2021 ◽

Author(s):

Eric Mull ◽

Brooke Gustafson ◽

Brent Adler ◽

Katelyn Krivchenia

Keyword(s):

Differential Diagnosis ◽

Acute Respiratory Distress Syndrome ◽

Abdominal Pain ◽

Respiratory Failure ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Case Reports ◽

Severe Constipation ◽

History Of

Acute respiratory distress syndrome (ARDS) is a disabling and potentially lethal syndrome requiring prompt recognition and urgent interventions to prevent morbidity and mortality[1]. Although constipation is not generally recognized as a cause for ARDS or usually listed within the differential diagnosis, there have been case reports describing such an association[2,3]. We present the case of a patient with history of intermittent constipation presenting with progressive abdominal pain and an acute abdomen that required emergent surgical fecal decompaction. This was followed by hypoxemic respiratory distress leading to respiratory failure in the setting of severe constipation and aspirated feculent material. To our knowledge, this is the first published case report describing aspirated feculent material in a child with respiratory failure due to ARDS.

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Factor VIII Inhibitors in Mild and Moderate-severity Haemophilia A

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615061 ◽

1998 ◽

Vol 79 (04) ◽

pp. 762-766 ◽

Cited By ~ 148

Author(s):

C.A. Ludlam ◽

B.T. Colvin ◽

F.G.H. Hill ◽

F.E. Preston ◽

N. Wasseem ◽

...

Keyword(s):

Factor Viii ◽

Tolerance Induction ◽

Haemophilia A ◽

Missense Mutations ◽

Bleeding Pattern ◽

Spontaneous Bleeding ◽

Familial Predisposition ◽

Inhibitor Development ◽

Acquired Haemophilia ◽

History Of

SummaryTwenty six patients with mild or moderate haemophilia A and inhibitors are described. The inhibitor was detected at a median age of 33 years, after a median of 5.5 bleeding episodes. This usually following intensive replacement therapy. The median presenting inhibitor titre was antihuman 11.6 BU/ml, antiporcine 1.45 BU/ml. Plasma basal factor VIII level declined from a median of 0.08 IU/ml to 0.01 IU/ml following the inhibitor development. This caused spontaneous bleeding in 22 and a bleeding pattern similar to acquired haemophilia in 17. Bleeding was often severe and caused two deaths.The inhibitor disappeared spontaneously, or following immune tolerance induction, in 16 cases after a median of 9 months (range 0.5-46), with a return to the original baseline VIIIC level and bleeding pattern accompanied inhibitor loss. The inhibitor persisted in the remainder of the cases over a median period of 99 months (range 17-433 months) of follow-up. Inhibitors are an uncommon complication of mild haemophilia which frequently persist and may be associated with severe, life-threatening, haemorrhage.Forty-one percent of treated haemophilic family members had a history of factor VIII inhibitors, suggesting a familial predisposition to develop inhibitors in these kindreds. Sixteen patients from 11 families were genotyped. Seven different missense mutations affecting the light chain were detected and two in the A2 domain. Five patients from three families had a mutation causing a substitution of Trp2229 by Cys in the C2 domain which appears to predispose to inhibitor formation since 7 of the 18 affected individuals have a history of inhibitor development.

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Acquired haemophilia A in women postpartum: management of bleeding episodes and natural history of the factor VIII inhibitor

European Journal Of Haematology ◽

10.1111/j.1600-0609.1997.tb00733.x ◽

2009 ◽

Vol 59 (2) ◽

pp. 105-109 ◽

Cited By ~ 32

Author(s):

J. J. Michiels ◽

K. Hamulyak ◽

H. K. Nieuwenhuis ◽

I. Novakova ◽

H. H. D. M. Vliet

Keyword(s):

Natural History ◽

Factor Viii ◽

Factor Viii Inhibitor ◽

Haemophilia A ◽

Acquired Haemophilia ◽

History Of ◽

Bleeding Episodes ◽

Viii Inhibitor

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Acquired Haemophilia A and Pregnancy/Postpartum – a Report From a European Registry

Blood ◽

10.1182/blood.v116.21.717.717 ◽

2010 ◽

Vol 116 (21) ◽

pp. 717-717 ◽

Cited By ~ 4

Author(s):

Laszlo Nemes ◽

Lilian Tengborn ◽

Peter W Collins ◽

Francesco Baudo ◽

Angela Huth-Kuehne ◽

...

Keyword(s):

Complete Remission ◽

Factor Viii ◽

Board Of Directors ◽

Research Funding ◽

Factor Vii ◽

Haemophilia A ◽

Red Cell ◽

Advisory Committees ◽

Acquired Haemophilia ◽

Baxter Healthcare

Abstract Abstract 717 Between 2003 and 2009 42 pregnant females were diagnosed with acquired haemophilia A (AHA) and included in the European Acquired Haemophilia A (EACH2) Registry. They constituted 8 % of the total number of admitted patients to the registry (n=501). In one female the diagnosis was made 36 days before delivery and the rest were diagnosed postpartum. One female had an autoimmune disorder, the others were without any associated disease. In 31 cases AHA occurred associated with the 1st pregnancy, in 7 the 2nd, in 2 the 3rd and in 2 the 4th pregnancy. Data are given as median and inter quartile ranges: Reference Age at pregnancy of interest 34 (30–37) Days after delivery until diagnosis 89 (25–180) Days between first abnormal APTT to diagnosis 1 (0–8) Factor VIII at diagnosis 2.5 (1–8) 50–200 IU/dL Anti Factor VIII antibody titre 7.8 (2.4–31.3) <0.4 BU/mL Hb 9.4 (7.5–12.9) 11.7–17.0 g/dL All the diagnoses were triggered by bleeds. Cause of bleed: spontaneous 24, trauma 1, surgery 4, peri postpartum 15. Site of bleed: deep (musculoskeletal, retroperitoneal) 14, haemarthroses 2, mucosa 18, skin 19, CNS none. In 11 females the bleeds started on day of diagnosis. In 22 females the bleeds started between 0 and 7 days before diagnosis and in 20 females the bleeds were reported to have started more than 7 days before the diagnosis suggesting a significant delay in diagnosis. In 25 the bleed was considered as severe (a drop of Hb >2 g/dL or received red cell transfusions) – in 7 of these no haemostatic treatment was given. 21/41 of first bleed required haemostatic treatment, 12 with rFVIIa (recombinant activated factor VII), 5 aPCC (activated prothrombin complex concentrate), 2 FVIII concentrate, 2 desmopressin. In addition, 6 received antifibrinolytics. Ten needed red cell transfusions. The bleeds were controlled in all cases and there was no fatality. First line immunosuppressive (IS) treatment: Regimen CR* n (%) NR** n (%) Treatment changed n (%) Days from start of IS Relapse n (%) Inhib <0.4 FVIII >70 IS stopped Steroids only n=31 22 (71) 8 (26) 1 (3) 47 (29–112) 40 (25–160) 105 (63–236) 2/20 (10) Steroids and Cytotoxics n=6 5 (83) 1 0 9, 35, 175, 261 12, 60, 175, 261 57, 60, 265, 363 0/5 Steroids and rituximab n=2 2 (100) 0 0 11, 76 11, 138 43, 53 0/2 * CR = complete remission i.e. FVIII >70 IU/dL and no antibodies ** NR = no complete remission Summing up, AHA is a rare but severe bleeding condition in pregnancy/postpartum and is often overlooked. The diagnosis should be considered when screening tests show an abnormal APTT which indicates an immediate specific coagulation analysis. Acute bleeds are effectively treated with rFVIIa or aPCC. Immunosuppression with steroids to eliminate the anti FVIII inhibitor activity should be instituted as soon as possible after confirmation of AHA and this treatment seems to give a better response compared to older patients with AHA. Disclosures: Nemes: Novo Nordisk: Tengborn: Novo Nordisk: Collins: NovoNordisk: Consultancy, Honoraria, The EACH2 registry was funded by Novonordisk; Baxter Healthcare: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Baudo:NovoNordisk: Consultancy, Honoraria, NovoNordisk fund the EACH2 registry, Speakers Bureau; Bayer Healthcare: Honoraria, Speakers Bureau. Huth-Kuehne:NovoNordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, NovoNordisk fund the EACH2 registry; Baxter Healthcare: Consultancy, Membership on an entity's Board of Directors or advisory committees. Knoebl:Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, NovoNordisk fund the EACH2 registry, Research Funding; Baxter Healthcare: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Marco:Novo Nordisk:Levesque:NovoNordisk:

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Progressive Intramuscular Haematoma in a 12-Year-Old Boy: A Case of Acquired Haemophilia A

Case Reports in Hematology ◽

10.1155/2018/6208597 ◽

2018 ◽

Vol 2018 ◽

pp. 1-3

Author(s):

Manori Gamage ◽

Sadeepa Weerasinghe ◽

Mohamed Nasoor ◽

A. M. P. W. Karunarathne ◽

Sashi Praba Abeyrathne

Keyword(s):

Factor Viii ◽

Soft Tissues ◽

Coagulation Factor ◽

Bleeding Disorder ◽

Haemophilia A ◽

Fviii Inhibitor ◽

Acquired Haemophilia ◽

High Antibody Titer ◽

History Of ◽

The Right

Acquired hemophilia A (AHA) is a rare bleeding disorder due to acquired antibodies against coagulation factor VIII (FVIII). It is rare in children less than 16 years old, and the incidence is 0.45/million/year. An otherwise healthy, 12-year-old boy was admitted to the ward with a history of swelling of the right and left forearms, for 1 day duration. He did not have any history of trauma or bleeding disorder. He had prolonged APPTT level with very high antibody titer against factor VIII. His gene expression for factor VIII was found to be normal. He was managed with FEIBA and recombinant FVII activated complexes and prednisolone 1 m/kg/day regime to control bleeding. AHA is associated with several underlying pathologies such as pregnancy, autoimmune diseases, malignancy, medications and infections; however, up to 50% of reported cases are idiopathic. In contrast to congenital haemophilia A, in which haemarthrosis is the hallmark clinical presentation, patients with AHA mainly bleed in to the skin, muscles, and soft tissues. High mortality rate of more than 20% is either to retroperitoneal or intracranial bleeds. Diagnosis is confirmed on isolated prolongation of activated partial thromboplastin time which does not normalize after addition of normal plasma, reducing the factor VIII levels with evidence of FVIII inhibitor activity. They have normal prothrombin time and platelet functions. Management of AHA involves two aspects, namely, eradication of antibodies and maintaining effective haemostasis during a bleeding episode.

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A case of serious bleeding

Clinical Management Issues ◽

10.7175/cmi.v5i2s.1106 ◽

2015 ◽

Vol 5 (2S) ◽

pp. 15-19

Author(s):

Irene Ricca ◽

Marisa Coggiola ◽

Silvia Destefanis ◽

Claudio Pascale

Keyword(s):

Mortality Rate ◽

Autoimmune Diseases ◽

Factor Viii ◽

Coagulation Factor ◽

The Elderly ◽

Severe Anaemia ◽

Severe Bleeding ◽

Haemophilia A ◽

Acquired Haemophilia ◽

History Of

Acquired haemophilia A (AHA) is a rare disorder with a high mortality rate. It occurs due to autoantibodies against coagulation factor VIII (FVIII) which neutralise its procoagulant function resulting in severe bleeding. This disease may be associated with autoimmune diseases, malignancies, infections or medications and occurs most commonly in the elderly. Diagnosis is based on the isolated prolongation of aPTT which does not normalise after the addition of normal plasma along with reduced FVIII levels. Treatment involves eradication of antibodies and maintaining effective haemostasis during bleeding. We report a case of a 76-year-old patient with a history of haemorrhage with severe anaemia. The article describes difficulties and complexities of clinical and therapeutic management of the patient.

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Acquired haemophilia – A diagnosis not to be missed

Acute Medicine Journal ◽

10.52964/amja.0198 ◽

2008 ◽

Vol 7 (2) ◽

pp. 70-72

Author(s):

S J Kitson ◽

◽

N F Grigoropoulos ◽

Keyword(s):

Autoimmune Diseases ◽

Factor Viii ◽

Coagulation Factor ◽

Clinical History ◽

Haemophilia A ◽

Haematological Malignancies ◽

Acquired Haemophilia ◽

Wide Range ◽

Life Threatening ◽

History Of

Acquired haemophilia is a rare, life threatening bleeding disorder characterised by the development of auto-antibodies to coagulation factor VIII. Diagnosis is based upon the clinical history of mucocutaneous haemorrhages combined with a selective prolongation of the APTT. The condition is associated with a wide range of conditions, such as autoimmune diseases , solid and haematological malignancies. Treatment involves controlling the bleeding manifestations and eliminating the inhibitor antibodies. Three cases from our recent practice are used to highlight the variable severity of this condition.

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Haemostatic Parameters and Lifestyle Factors in Elderly Men in Italy and The Netherlands

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650592 ◽

1996 ◽

Vol 76 (03) ◽

pp. 411-416 ◽

Cited By ~ 8

Author(s):

Fransje C H Bijnen ◽

Edith J M Feskens ◽

Simona Giampaoli ◽

Alessandro Menotti ◽

Flaminio Fidanza ◽

...

Keyword(s):

Alcohol Use ◽

The Netherlands ◽

Antithrombin Iii ◽

Lifestyle Factors ◽

Activated Partial Thromboplastin Time ◽

Factor Vii ◽

Fat Intake ◽

Factor X ◽

Elderly Men ◽

History Of

SummaryThe association between plasma fibrinogen, factor VII, factor X, activated partial thromboplastin time, antithrombin III and the lifestyle factors cigarette smoking, alcohol use, fat intake and physical activity was assessed in 802 men aged 70-90 years in Zutphen (The Netherlands), Montegiorgio and Crevalcore (Italy).Smoking was positively associated with fibrinogen, also after adjustment for other lifestyle factors, age, use of anticoagulants and aspirin like drugs, body mass index, and history of myocardial infarction. Alcohol use was associated with increased levels of factor X and decreased levels of antithrombin III. Fat intake was positively associated with antithrombin III. Between cohorts, considerable differences were observed in levels of haemostatic parameters and the lifestyle factors. Compared to the mediterranean cohorts the Zutphen cohort showed the highest levels of fibrinogen and factor VII. Differences in lifestyle factors could, however, not explain differences between cohorts in levels of any of the haemostatic parameters, despite the observed associations between lifestyle factors and haemostatic parameters.

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