Case Report

Fatal Bleeding Due to Acquired Factor IX and X Deficiency: A Rare Complication of Primary Amyloidosis; Case Report and Review of the Literature Stephanie Ericson,1 Nihar Shah,2 Justin Liberman,1 David M. Aboulafia3,4 Clinical Practice Points  Amyloid light chain (AL) amyloidosis is a clonal plasma

cell disorder, resulting in tissue and organ immunoglobulin deposits. Often multiple organ systems are involved, but occasionally it can impact predominantly one organ.  Extensive amyloid involvement of the spleen can present with an acquired factor deficiency associated hemorrhage due to the selective clotting factor adsorption of the amyloid fibrils.  Life-threatening bleeding due to deficiencies of individual or combinations of clotting factors is, fortunately, a relatively unusual problem in the context of AL amyloidosis, but presents unique diagnostic and therapeutic challenges. Though publications documenting successful resolution of amyloidosis-associated factor deficiency after splenectomy are scarce (seven cases reviewed in our study20-26), the present lack of robust alternative therapies suggests consideration

of splenectomy in the case of refractory bleeding with exhausted conservative measures in the context of biopsy-negative but clinically likely amyloidosis (findings of MGUS, splenomegaly, and unexplained acquired coagulation factor deficiencies).  In the absence of tissue diagnosis, other rare causes of factor X deficiency should be considered, including liver disease, certain tumors (spindle cell thymoma, renal/adrenal carcinoma, gastric carcinoma), and mycoplasma pneumonia (a rare association with transient factor X deficiency).  The low sensitivity associated with tissue biopsies in splenic predominant amyloidosis may be due to lower amyloid burden in other, more commonly biopsied tissues. As splenectomy itself can be a high-risk procedure, obtaining multiple fat aspirates looking for AL deposition in an effort to obtain tissue proven diagnosis is a prudent and low-risk diagnostic necessity.

Clinical Lymphoma, Myeloma & Leukemia, Vol. 14, No. 3, e81-6 ª 2014 Elsevier Inc. All rights reserved. Keywords: Acquired factor deficiency, AL amyloidosis, Combined factor IX and X deficiency state, MGUS, Splenectomy

Introduction Primary light chain (AL) amyloidosis is a disorder of clonal plasma cells resulting in tissue and organ immunoglobulin deposits; it often involves multiple organ systems, but can occasionally affect primarily 1 organ. Diagnostic delay is common in AL amyloidosis because of the rarity of this condition and nonspecific symptoms 1

Division of Internal Medicine, Virginia Mason Medical Center, Seattle, WA Division of Gastroenterology, Virginia Mason Medical Center, Seattle, WA 3 Division of Hematology and Oncology, Virginia Mason Medical Center, Seattle, WA 4 Division of Hematology, University of Washington, Seattle, WA 2

Submitted: Jun 3, 2013; Accepted: Aug 28, 2013; Epub: Nov 27, 2013 Address for correspondence: David M. Aboulafia, MD, Division of Hematology/ Oncology, Virginia Mason Medical Center, 110 Ninth Avenue, PO Box 900 (C2-HEM), Seattle, WA 98111 Fax: 206-223-2382; e-mail contact: [email protected]

2152-2650/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clml.2013.08.007

such as fatigue, weight loss, and paresthesias. Extensive amyloid involvement of the spleen can present with a bleeding diathesis and hemorrhage due to the selective clotting factor adsorption of the amyloid fibrils.1 Herein, we present the case of a 62-year-old healthy man who presented with uncontrolled retroperitoneal bleeding, with suspected amyloidosis based on the presence of monoclonal gammopathy of undetermined significance and combined acquired factors IX and X deficiencies; however, antemortem biopsies were negative, with a definitive diagnosis secured postmortem. Using a MedLine search, we identified an additional 5 cases of combined factor IX and factor X deficiencies attributed to AL amyloidosis.2-5 Only 2 of the 6 cases had biopsy proven amyloidosis before necroscopy, with all showing extensive hepatosplenic involvement at autopsy. In each instance, the patients presented with significant bleeding and laboratory studies most notable for prolongation of

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Fatal Bleeding in Factor IX and X Deficiency prothrombin (PT) and partial thromboplastin (PTT) times in the absence of an acquired inhibitor of coagulation. The median age of these patients was 57 years (range, 42-66 years). Five of them died, 4 from bleeding complications, and 1 from chemotherapyassociated hepatic failure due to reactivation of hepatitis B. Three of the 6 were treated with chemotherapy and supportive blood products, and the others with supportive blood products alone. Management of bleeding in this context is profoundly problematic, although the available literature hints at the benefit of splenectomy to reverse acquired coagulation factor deficiencies associated with AL amyloidosis. Amyloidosis refers to the extracellular tissue deposition of fibrils composed of low molecular-weight subunits of a variety of normal serum proteins. On x-ray diffraction, these fibrils have a predominantly antiparallel b-pleated sheet configuration identified on biopsy specimens by their characteristic appearance on electron microscopy and by their ability to bind Congo red and thioflavin T, leading to green birefringence in polarized light and producing an intense yellow-green fluorescence, respectively.6,7 Primary light chain amyloidosis, the most common form of systemic amyloidosis, results in the accumulation of monoclonal light chains in various tissues and organs. Affected patients might have amyloidosis alone or in association with other plasma cell dyscrasias, such as monoclonal gammopathy of uncertain significance (MGUS), multiple myeloma, or non-Hodgkin lymphoma. Prognosis is poor, with an overall 5-year survival of 20%, and a median survival of just 20 months.8 Age-adjusted incidence of AL amyloidosis is estimated at 5.1 to 12.8 cases per million person-years in the United States, with an incidence rate of 0.09% to 0.8% in hospitalized patients and 0.4% to 0.5% in autopsy series.9,10 AL amyloidosis most commonly affects men and is diagnosed most frequently in patients in their sixth or seventh decade of life. As a systemic disorder, AL amyloidosis can present with a variety of signs and symptoms, including peripheral neuropathy, hepatosplenomegaly, congestive heart failure, nephrotic range proteinuria, edema, and carpal tunnel syndrome. Although most patients have multisystem amyloid deposition, they often show clinical stigmata of predominantly 1 organ being affected.11 Although hepatic deposition occurs in half of cases, it is usually clinically silent, and the liver is rarely the dominant organ.12,13 Unfortunately, delayed diagnosis is common because of the nonspecific nature of clinical presentations and failure of health care providers to include it in the differential diagnosis.10 Bleeding in AL amyloidosis is common and multifactorial, resulting from vessel fragility from amyloid infiltration, hyperfibrinolysis, platelet dysfunction, and uremia.8 Fulminant bleeding, however, is usually secondary to acquired factor deficiencies; only 2.3% of patients with AL amyloidosis will present with significant bleeding.8 Herein, we describe the case of a patient with uncontrolled hemorrhage due to severe acquired combined deficiency of coagulation factors IX and X. We review the literature of similar cases, focusing on patient demographic characteristics, clinical presentation, mode of diagnosis, and treatment outcome. We also consider the risks and benefits of splenectomy for the treatment of factor deficiencies attributed to AL amyloidosis.

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Figure 1 Pelvic Computed Tomography Scan Showed an Intraabdominal Hemorrhage. Findings of Abnormal Density Posterior to the Head of the Pancreas and Descending Duodenum With Irregular Margins, Consistent With Blood or Soft Tissue, Measuring Approximately 3.7 3 5.8 3 7.1 cm, Suspicious for Active Hemorrhage

Case Report A previously healthy 62-year-old man presented to the Emergency Department (ED) with right-sided abdominal pain. Two months earlier he had sought medical attention for vague abdominal discomfort, mild fatigue, and easy bruising. His initial evaluation was remarkable only for the presence of microscopic hematuria, which prompted his physician to obtain a computed tomograpy (CT) scan of the abdomen and pelvis in conjunction with intravenous pyelogram followed by bladder cystoscopy. No findings were identified to suggest nephrolithiasis or malignancy. In the ED, the patient was hemodynamically stable. His general exam was notable only for mild abdominal distention and tenderness, without guarding, rebound, or hepatosplenomegaly. Some mild bruising was present on his right antecubital fossa at a site where an intravenous line was inserted. A complete blood count and serum electrolytes were within normal limits. Liver function tests showed a mildly elevated level of aspartate aminotransferase of 51 IU/L (normal 10-40 IU/L), but normal alanine aminotransferase, alkaline phosphatase, bilirubin, protein, and albumin levels. Fibrinogen, thrombin time, and a D-dimer were also within normal limits, but PT, international normalized ratio (INR), and PTT were elevated (PT was 55.8 seconds, normal: 10.8-13.1 seconds; INR was 6.2, normal: 0.9-1.2; PTT was 78.3 seconds, normal: 25.0-39.0 seconds). He was admitted to the hospital after an abdominal and pelvic CT scan showed intraabdominal hemorrhage (Fig. 1). The patient’s medical history was significant for hypertension and hyperlipidemia. Daily medications included simvastatin, hydrochlorothiazide-triamterene, and 81 mg aspirin. There was no personal or family history of coagulopathy. He had a 20 pack-year

Stephanie Ericson et al history of smoking but had quit 25 years ago, and drank alcohol in moderation. Additional laboratory studies were collected, including 1:1 mixing studies for PT and PTT, which led to normalization of both clotting times. Coagulation factor levels were notable for decreased factor IX level of 22% (normal, 60%-150%) and factor X level of 1% (normal, 50%-150%). Quantitative immunoglobulin levels consisted of an immunoglobulin (Ig)A of 72 g/dL (normal, 101-645 g/dL), an IgG of 434 g/dL (normal, 540-1822 g/dL), and an IgM of 28 (normal, 22-293). Beta-2 microglobulin was within normal limits. Free serum kappa light chain was within normal limits at 7.81 mg/L (normal, 3.3-19.4 mg/L), but lambda light chain was elevated at 138.78 mg/L (normal 5.7-26.3 mg/L), corresponding to a monoclonal IgG lambda band of 0.2 g/dL (normal, 0.0 g/dL) according to serum protein immunoelectrophoresis (SPIEP). Within 12 hours of admission, the patient’s abdomen became markedly distended, resulting in respiratory distress for which he required mechanical ventilation. An emergent CT scan of the abdomen revealed contrast extravasation near the head of the pancreas, consistent with active hemorrhage. Two guided embolizations of the gastroduodenal artery were performed in the Interventional Radiology Department over the next 8 hours but retroperitoneal bleeding persisted. Over the course of the next 72 hours he received a total of 9 units of packed red blood cells, 11 units of fresh frozen plasma (FFP), a 10-pack of platelets, 8 units of cryoprecipitate, and 6039 units of intravenous prothrombin complex. Despite these interventions, there was little improvement in his coagulation profile and he continued to actively bleed. Because of worsening abdominal distension he was taken to surgery for an exploratory and decompressive laparotomy. Four liters of blood were evacuated from his abdominal cavity. Peritoneal and omental biopsies were collected (liver biopsy was deferred because of the concern for increased bleeding risk and hepatic rupture) but microscopic evidence of amyloidosis was not identified from these samples. Intraoperatively he received factor 8 inhibitor bypass Figure 2 Massive Deposition of Amyloid Within Liver and Spleen. Liver Sinusoids Replaced by Pink-Staining Amyloid, Leaving Scattered Individual and Small Groups of Hepatocytes (Hematoxylin and Eosin [H % E], Magnification 3400). Inset: Nodules of Amyloid are Evident in the Spleen (H & E, Magnification 3100)

activity (FEIBA) antiinhibitor coagulation complex. This was continued postoperatively, but within hours he became hypoxic and was diagnosed with extensive pulmonary emboli and bilateral lower extremity deep vein thrombosis. FEIBA was thus discontinued and an inferior vena cava filter was placed by an interventional radiologist. For the next week, his condition remained tenuous and his course complicated by ventilator-associated Klebsiella oxytoca pneumonia, hypotension, ongoing bleeding, and rapidly worsening renal and hepatic function. By hospital day 14, the patient had received a total of 18,476 units of nanofiltered factor IX complex for persistent gastrointestinal and retroperitoneal bleeding. In the context of medical futility and after further discussions with his family, no additional interventions were pursued and he died shortly thereafter. Autopsy findings included massive deposition of amyloid within liver and spleen (Fig. 2 and inset). Monotypic lambda staining of the plasma cells in the bone marrow accounted for 15% of nucleated cell forms.

Discussion In summary, our patient presented with abdominal pain and microscopic hematuria, followed shortly thereafter by massive and uncontrolled retroperitoneal hemorrhage. Despite treatment with procoagulant factors, his clinical course was complicated by persistent bleeding, lower extremity deep vein thrombosis, and pulmonary emboli, hypotension, multiorgan failure, and ultimately, death. Although coagulopathy can occur in the context of AL amyloidosis, bleeding is usually mild. The reasons for bleeding are protean and might include acquired von Willebrand disease, thrombocytopenia, renal insufficiency, abnormal fibrin polymerization, hyperfibrinolysis, vessel wall fragility associated with amyloid deposition, and acquired deficiencies of various coagulation factors.8,14 Less than 5% of AL amyloidosis cases present with factor X deficiency; yet, at a frequency of 8.7% it is the most common factor deficiency associated with AL amyloidosis.8,15-18 Other factor deficiencies, including isolated deficiencies of factors II, V, VII, IX, and combined deficiencies of factors VII and X or V and X have been reported infrequently in the literature.19 Combined deficiencies of factors IX and X, as seen in our case, are particularly rare events. We searched PubMed for reports published before 2013, with the search terms “amyloidosis” and “factor IX and X deficiency.” We did not limit our search by language, and identified only 5 additional cases of combined factors IX and X deficiency associated with amyloidosis.2-5 In our literature review, the median age at diagnosis was 57 years (range, 43-66 years) and 4 of the patients with combined factors IX and X deficiency were male (Table 1).2-5,13-16 In each instance, patients noted weight loss; in 3 instances, a weight loss greater than 10% of total body weight preceded the diagnosis of amyloidosis, and in 1 instance weight loss was dramatic—greater than 40 pounds in the antecedent 6 months.2 Fatigue was an ubiquitous complaint, and 3 of the patients described paresthesias or dysesthesias in association with MGUS. Five had MGUS identified on SPIEP and in each instance this was an IgG kappa of less than 0.6 g/dL.2-5 Bleeding complications were diverse, ranging from ecchymosis and easy bruising to significant hemorrhage involving the retroperitoneal cavity, uterus, intramuscular shoulder, and the

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Clinical Presentation/ Age Time to (Years)/Sex Diagnosis Site of Bleeding Splenomegaly Proteinuria RI aPTT Index Patient 1Current 62/M

FX

F IX

MCB

BMB

Antemortem Amyloid Biopsy Results

Treatment

Cause of D eath

Postmortem Biopsy: Amyloid Deposition Sites

Study

2 Months Abdominal pain, (at autopsy) fatigue, hematuria

IgG l 0.2 Postmortem: Peritoneal tissue 15% plasma negative for cells, positive amyloid for amyloid

N

x

N

78

1%

22%

Y, hyposplenism (Howell-Jolly bodies)



x

46

6%

15%

No light chains

x

x

x

45

7%

16%

IgG l

35%

N



Y

54

11%

48%

IgG l

9% Plasma cells

Y



Y

69.8

1 Year

Nausea, vomiting, and cachexia

13% Plasma cells

Patient 314 43/F

>6 Months Bleeding after hysterectomy

Patient 415 52/M

x

Abdominal pain

Patient 513 66/M

>6 Months Fatigue, weight loss, SOB, chest pain

Postmortem: Abdominal fat Supportive 15% plasma pad and rectal cells biopsies negative for amyloid

Patient 616 58/M

1 Month

Right shoulder hematoma

12% Plasma cells

Gastric biopsy positive for amyloid

Melphalan, prednisone, Alive by report stopped treatment due to BM toxicity

x

Abbreviations: aPTT ¼ activated prothrombin time; BMB ¼ bone marrow biopsy; BM = bone marrow; F ¼ female; FEIBA = factor eight inhibitor bypass activity; F IX ¼ factor IX; F X ¼ factor X; GI ¼ gastrointestinal; GIB ¼ gastrointestinal bleed; MCB ¼ monoclonal bands; N ¼ no; RI ¼ renal insufficiency; SOB ¼ shortness of breath; x ¼ not indicated in case report; Y ¼ yes.

Fatal Bleeding in Factor IX and X Deficiency

Clinical Lymphoma, Myeloma & Leukemia June 2014

Table 1 Patient Characteristics

Stephanie Ericson et al gastrointestinal and genitourinary systems. All of the patients had significant prolongations of the PT and PTT times. In all but 1 instance, glomerular filtration was well preserved, though proteinuria was common. All 6 patients had amyloidosis involving the spleen at necroscopy.2-5 Delayed diagnosis is common in AL amyloidosis because of nonspecific clinical presentations and low diagnostic sensitivity of antemortem biopsy. In only 2 instances was a diagnosis of AL amyloidosis secured antemortem, despite what later proved to be extensive multiorgan involvement. Of those 2, 1 diagnosis was secured by bone marrow biopsy, and the other by gastric biopsy. Even in the context of a significant coagulation factor deficiency and active bleeding, there was a delay in tissue diagnosis of amyloidosis by 6.5 months (range, 2 to > 12 months).2-5 Liver function tests are usually normal or mildly elevated in patients with hepatic amyloidosis, with elevation of alkaline phosphatase and gammaglutyl transferase being the most common finding.13 Considering the challenges of establishing a biopsy-proven diagnosis of AL amyloidosis, including concerns of an increased bleeding risk from percutaneous liver biopsy, empiric splenectomy should be considered when clinical evidence supports AL amyloidosis-associated factors X or combined IX and X deficiencies if conservative measures fail to resolve life-threatening hemorrhage. In several case reports, such a course led to resolution of isolated factor X deficiency in amyloidosis.20-26 In the most notable instance, a 50-year-old woman with AL amyloidosis underwent hysterectomy for menorrhagia.26 She suffered severe postoperative intraabdominal bleeding. Exploratory laparotomy revealed a bleeding splenic vein, for which she underwent splenectomy, which resulted in normalization of factor X levels and resolution of bleeding. In another instance, a 49-year-old man with amyloidosisassociated factor X deficiency showed no improvement in factor X levels after receiving melphalan and prednisone chemotherapy.21 He underwent laparotomy for control of severe gastrointestinal bleeding. Suspecting splenic factor X sequestration, his physician performed a splenectomy, which also resulted in resolution of factor X deficiency and maintenance of normal levels during the subsequent 30 months.21 In an additional 5 instances, splenectomy led to normalization of factor X levels.20-26 All patients were free of perioperative bleeding complications with the use of either high doses of FFP, recombinant FVIIa, or prothrombin complex concentrate.20-26 Splenectomy appears to be an effective option in this context, although case reports documenting this intervention are scarce.20-27 In these reports, perioperative management with recombinant factor VIIa was successfully used to minimize bleeding.22,23,28 Unfortunately, it does carry a substantial risk of thrombosis (in a review of randomized controlled trials this complication occurred in 11% of instances in which factor VIIa was used).20,27 Life-threatening bleeding due to deficiencies of individual or combinations of clotting factors is, fortunately, a relatively unusual problem in the context of AL amyloidosis. Splenectomy should be considered in the case of profound bleeding that is not improved with conservative measures. This should also be considered in biopsynegative amyloidosis with the finding of MGUS, splenomegaly, and otherwise unexplained acquired coagulation factor deficiencies.

In making a treatment decision in the absence of tissue diagnosis, other rare causes of factor X deficiency should be considered, including liver disease, certain tumors (spindle cell thymoma, renal/ adrenal carcinoma, gastric carcinoma), and mycoplasma pneumonia (a rare association with transient factor X deficiency).15 The low sensitivity associated with tissue biopsies revealed in the cases described herein might be due to predominant splenic involvement with lower amyloid burden in other, more commonly biopsied tissues. Because splenectomy itself can be a high-risk procedure, obtaining multiple fat aspirates to identify AL deposition in an effort to obtain tissue proven diagnosis is a low-risk option.29,30 Treatment of amyloidosis with conventional alkylator and steroidbased regimens, or more novel options which incorporate steroids with lenalidomide or thalidomide and the first-in-class proteasome inhibitor bortezomib have been associated with improved outcomes even in the context of advanced disease. Rarely, patients with extensive AL amyloidosis are candidates for chemotherapy followed by autologous stem cell reinfusion. New treatment modalities involving small interfering RNA and gene conversion strategies have also shown experimental success in reducing the synthesis of amyloidogenic light chains.31 Another strategy is to promote fibril reabsorption; a high-affinity ligand of serum amyloid P component (SAP), the bis-D-proline compound CPHPC, has been shown to deplete circulating levels of SAP by more than 90%.32

Conclusion Diagnosis of amyloidosis remains challenging and more research is needed to better define the efficacy and safety of splenectomy as a treatment of potentially fatal hemorrhage in amyloidosis-associated coagulation factor deficiencies.

Disclosure All authors have no conflicts of interest.

References 1. Furie B, Voo L, McAdam KP, et al. Mechanism of factor X deficiency in systemic amyloidosis. N Engl J Med 1981; 304:827-30. 2. Figler TJ, Keshavarzian S, Naund TC. Retroperitoneal amyloidosis, factor IX and X deficiency, and gastrointestinal bleeding. Abdom Imaging 1994; 21:266-8. 3. McPherson RA, Onstad JW, Ugoretz RJ, et al. Coagulopathy in amyloidosis: combined deficiency of factors IX and X. Am J Hematol 1977; 3:225-35. 4. Hanley JP, MacLean FR, Evans JL, et al. Hemorrhagic lymphadenopathy as a presenting feature of primary AL amyloidosis. Pathology 2000; 32:21-3. 5. Suhara Y, Mine H, Miura S, et al. Case of primary amyloidosis complicated with intramuscular hemorrhage and Factor IX and X deficiencies [in Japanese]. Nihon Naika Gakkai Zasshi 1991; 80:621-2. 6. Bilar A, Selmi C, Naguwa SM, et al. Current concepts on the immunopathology of amyloidosis. Clin Rev Allergy Immunol 2010; 38:97-106. 7. Picken MM. Amyloidosis e where are we now and where are we heading? Arch Pathol Lab Med 2010; 134:545-51. 8. Gertz MA, Buadi FK, Zeldenrust SR, et al. Immunoglobulin light chain amyloidosis. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. Hematology, Basic Principles and Practice, 6th ed. Elsevier Saunders, Philadelphia. 2012:350-374. 9. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med 1997; 337:898-909. 10. Black RM, Alfred HJ, Pang-Yen F, et al. Amyloidosis and light chain deposition. In: Clinical Problems in Nephrology. Little Brown, Boston. 1996:309-314. 11. Comenzo RL, Zhang Y, Martinez C, et al. The trophism of organ involvement in primary systemic amyloidosis; contributions of IgV 9L. Blood 2001; 98:714-20. 12. Gillmore JD, Lovat LB, Hawkins PN. Amyloidosis and the liver. J Hepatol 1999; 30(suppl 1):17-33. 13. Gertz MA, Kyle RA. Hepatic amyloidosis (primary [AL], immunoglobulin light chain): the natural history in 80 patients. Am J Med 1988; 85:73-80. 14. Kapoor P, Singh E, Radhakrishnan P, et al. Splenectomy in plasma cell dyscrasias: a review of the clinical practice. Am J Hematol 2006; 81:946-54.

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- e85

Fatal Bleeding in Factor IX and X Deficiency 15. Uprichard J, Perry DJ. Factor X deficiency. Blood Rev 2002; 16:97-110. 16. Gertz MA, Lacy MQ, Dispenzieri A. Amyloidosis: recognition, confirmation, prognosis, and therapy. Mayo Clin Proc 1999; 74:490-4. 17. Choufani EB, Sanchorawala V, Ernst T, et al. Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy. Blood 2001; 97:1885-7. 18. Mumford AD, O’Donnell J, Gillmore JD, et al. Bleeding symptoms and coagulation abnormalities in 337 patients with AL-amyloidosis. Br J Haematol 2000; 110:454-60. 19. Sucker C, Hetzel GR, Grabensee B, et al. Amyloidosis and bleeding: pathophysiology, diagnosis, and therapy. Am J Kidney Dis 2006; 47:947-55. 20. Rosenstein ED, Itzkowitz SH, Penziner AS, et al. Resolution of factor X deficiency in primary amyloidosis following splenectomy. Arch Intern Med 1983; 143:597-9. 21. Greipp PR, Kyle RA, Bowie EJ. Factor X deficiency in primary amyloidosis: resolution after splenectomy. N Engl J Med 1979; 301:1050-1. 22. Boggio L, Green D. Recombinant human factor VIIa in the management of amyloid-associated factor X deficiency. Br J Haematol 2001; 112:1074-5. 23. Ma JF, Coutre SE, Curet MJ, et al. Refractory hematuria from amyloidosis successfully treated by splenectomy. Urology 2006; 67:1085.e13-5. 24. Bohrer H, Waldherr R, Martin E, et al. Splenectomy in an uraemic patient with acquired factor X deficiency due to AL amyloidosis. Nephrol Dial Transplant 1998; 13: 190-3.

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25. Cohen D, Mordechai P, Franklin EC, et al. Characterization of amyloid deposits and P component from a patient with factor X deficiency reveals proteins derived from a l VI light chain. Am J Med 1983; 74:513-5. 26. Korsan-Bengsten K, Hjort PF, Ygge J. Acquired factor X deficiency in a patient with amyloidosis. Thromb Diath Haemorrh 1962; 7:558-66. 27. Levi M, Levy JH, Andersen HF, et al. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med 2010; 363:1791-800. 28. Takabe K, Holman PR, Herbst KD, et al. Successful perioperative management of factor X deficiency associated with primary amyloidosis. J Gastrointest Surg 2004; 8:358-62. 29. Duston MA, Skinner M, Meenan RF, et al. Sensitivity, specificity, and predictive value of abdominal fat aspiration for the diagnosis of amyloidosis. Arthritis Rheum 1989; 32:82-5. 30. van Gameren II, Hazenberg BP, Bijzet J, et al. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis and its utility in clinical practice. Arthritis Rheum 2006; 54:2015-21. 31. Ohno S, Yoshimoto M, Honda S, et al. The antisense approach in amyloid light chain amyloidosis: identification of monocloncal Ig and inhibition of its production by antisense oligonucleotides in in vitro and in vivo models. J Immunol 2002; 169:4039-45. 32. Pepys MB, Herbert J, Hutchinson WL, et al. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature 2002; 417:254-9.

Fatal bleeding due to acquired factor IX and X deficiency: a rare complication of primary amyloidosis; case report and review of the literature.

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