Analysis of seven cases of multiple myeloma with initial manifestation of bleeding / 中华内科杂志

A retrospective analysis of 7 patients of multiple myeloma (MM) with initial manifestation of bleeding and coagulation abnormalities were performed. Clinical manifestations, laboratory and imaging examinations were collected. The activity of coagulation factors was measured before the treatment. Single factor X deficiency was seen in one patient. Two cases had factor Ⅶ deficiency, while four other patients had multiple factor deficiency. The time from onset of symptoms to diagnosis ranged from 2 to 10 months. After anti-MM treatment started and plasma or coagulation factors were transfused, the prolonged coagulation time returned to normal from 28-84 days. Most of these patients presented large, deep and multiple sites of hematoma, which caused concerns of bone marrow puncture and may direct to other differential diagnoses. This is helpful to improve physicians′ understanding of the special clinical characteristics in MM patients.

Amyloidosis Presenting as Severe Bleeding Diathesis

Bleeding is one of the rare presentations of Amyloidosis. The mechanism behind spontaneous or peri- interventional bleeding in patients of amyloidosis is complex and involves multiple co-existing factors like coagulation factor deficiency, abnormal synthesis of coagulation factors due to advanced liver dysfunction, acquired Von Willebrand disease, platelet dysfunction, amyloid angiopathy and other unknown mechanisms. We present a case of middle aged female, presenting with spontaneous retroperitoneal haemorrhage, on further investigations was found to have systemic amyloidosis and secondary severe factor X deficiency (2.7 % of normal by one stage factor assay method). Factor X deficiency (both inherited and acquired) is known to present with the most severe bleeding phenotype. The management option for such acute spontaneous haemorrhage is limited and mostly supportive in nature. Definitive treatment is directed towards the primary pathology and requires chemotherapy and hematopoietic stem cell transplantation.

Impact of Rare Bleeding Disorders during Pregnancy on Maternal and Fetal Outcomes: Review of 29 Pregnancies at a Single Center / Impacto de distúrbios hemorrágicos raros durante a gestação na mãe e no feto: revisão de 29 gestações em um único centro

ABSTRACT Objective: This study aims to give information about the relationship between different types of factor deficiencies and maternal/obstetric outcomes. Methods We retrospectively reviewed the medical records of eight women with factor deficiency disorders. The demographic and clinical features of the patients after their last pregnancies were registered retrospectively. Results: There were 29 pregnancies among the 8 patients. The spontaneous abortion rate was relatively high in two patients with factor XIII deficiency (80% and 57.1%) compared with the other factor deficiency groups. There were 16 births, which included 1 set of twins, and 2 deaths (1 stillbirth and 1 postpartum exitus occurred in the same patient). Intrauterine growth restriction was noted in five cases; four of these occurred in factor X deficiency cases. The mean decrease in hemoglobin level of all patients after birth was 1.7 g/dL (range, 0.2-3.6 g/dL). Red blood cell transfusion was required only in one case of factor XIII deficiency. Conclusions: There is currently no consensus on the pregnancy management of women with factor deficiencies because of the limited knowledge due to the rarity of such disorders. Labor should be managed in a dedicated unit with a team consisting of an obstetrician, a hematologist, an anesthesiologist, a midwife, and a pediatrician to minimalize the complications.

RESUMO Objetivo: O presente estudo objetiva fornecer informações sobre a relação entre diferentes tipos de deficiências de fator e resultados obstétricos e maternais. Métodos Análise retrospectiva de registros médicos de oito mulheres com deficiências de fator. Dados demográficos e clínicos das pacientes após sua última gestação foram obtidos. Resultados: Vinte e nove gestações ocorreram entre as oito pacientes. As taxas de abortos espontâneos foram relativamente altas em duas pacientes com deficiência de fator XIII (80% e 57,1%) se comparadas aos demais grupos de deficiências de fator. Ocorreram dezesseis nascimentos, sendo que um deles foi o de um par de gêmeos, e dois óbitos (um natimorto e um pós-parto na mesma paciente). Restrição de crescimento intrauterino foi identificada em cinco casos, sendo quatro destes com deficiência de fator X. A principal baixa em nível de hemoglobina entre todas as pacientes após o parto foi de 1,7 g/dL (variação, 0,2-3,6 g/dL). Transfusão de hemácias foi necessária apenas em um caso com deficiência de fator XIII. Conclusão: Não há consenso atualmente para o manejo de gestantes com deficiências de fator em função do conhecimento limitado, dada a raridade de tais condições. O parto deve ocorrer em uma unidade específica com uma equipe composta de obstetra, hematologista, anestesista, parteira, e pediatra para minimizar as complicações

Cirurgia oral em pacientes hemofílicos: cuidados que o cirurgião-dentista precisa ter / Oral surgery in hemophilic patients: guidelines for the dental surgeon

A hemofilia é um distúrbio hemorrágico hereditário comum, caracterizada como uma desordem cromossômica ligado ao fator X, causando uma variedade de mutações no fator VIII (hemofilia A) e IV (hemofilia B). O objetivo do presente estudo foi, atráves de uma revisão da literatura, enfatizar os cuidados que o cirurgião-dentista deve ter na cirurgia oral com pacientes hemofílicos. Atualmente, quando se segue um protocolo, com fatores de reposição, antibiótico profilático, medidas hemostáticas locais e técnicas operatórias adequadas, o risco de hemorragia para pacientes hemofilícos, durante ou após cirurgias orais, diminui significativamente.

Hemophilia A is a common inherited bleeding disorder, characterized as a chromosome X-linked recessive bleeding factor, causing a variety of mutations in factors VIII (hemophilia A) and IV (hemophilia B). The aim of this study was, through a literature review, to emphasize the care with hemophilic patients in oral surgery. When an adequate protocol is followed, with spare factors, antibiotic prophylaxis, local hemostatic and appropriate surgical technique, the risk of hemorrhage for hemophilic patients during or after oral surgery signifi cantly decreases.

Acquired Factor X Deficiency in Light Chain Amyloidosis: A Report of 2 Korean Cases / 대한진단검사의학회지

Amyloidosis is a heterogeneous group of diseases in which misfolding of extracellular proteins is the pathogenic factor. Light chain amyloidosis (AL) is the most common form of amyloidosis, and the causative proteins in AL are the immunoglobulin light chains produced by clonal plasma cells. Hemorrhagic events, ranging from mild subcutaneous hemorrhage to life-threatening bleeding, account for a significant proportion of morbidities and mortality in AL patients. Deficiency of factor X from deposition into amyloid fibrils has been reported to be the most common acquired factor deficiency in AL. We herein report 2 patients with acquired factor X deficiency in AL. A 55-yr-old woman with AL had a prolonged prothrombin time (PT) and an activated partial thromboplastin time (aPTT) of 2.51 International Normalized Ratio (INR) and 75.1 sec, respectively, which were corrected on mixing with normal plasma. Factor X activity was markedly decreased at 5%. The other patient was a 67-yr-old man with AL with a PT of 1.63 INR and an aPTT of 50.3 sec, which were corrected on mixing with normal plasma. Factor X activity was decreased at 17%. Neither of the patients had apparent hemorrhagic manifestations. Identification of acquired factor deficiency and timely coagulation tests are needed in the diagnostic workup and management in AL.

Acquired Factor X Deficiency in Light Chain Amyloidosis: A Report of 2 Korean Cases / 대한진단검사의학회지

Amyloidosis is a heterogeneous group of diseases in which misfolding of extracellular proteins is the pathogenic factor. Light chain amyloidosis (AL) is the most common form of amyloidosis, and the causative proteins in AL are the immunoglobulin light chains produced by clonal plasma cells. Hemorrhagic events, ranging from mild subcutaneous hemorrhage to life-threatening bleeding, account for a significant proportion of morbidities and mortality in AL patients. Deficiency of factor X from deposition into amyloid fibrils has been reported to be the most common acquired factor deficiency in AL. We herein report 2 patients with acquired factor X deficiency in AL. A 55-yr-old woman with AL had a prolonged prothrombin time (PT) and an activated partial thromboplastin time (aPTT) of 2.51 International Normalized Ratio (INR) and 75.1 sec, respectively, which were corrected on mixing with normal plasma. Factor X activity was markedly decreased at 5%. The other patient was a 67-yr-old man with AL with a PT of 1.63 INR and an aPTT of 50.3 sec, which were corrected on mixing with normal plasma. Factor X activity was decreased at 17%. Neither of the patients had apparent hemorrhagic manifestations. Identification of acquired factor deficiency and timely coagulation tests are needed in the diagnostic workup and management in AL.

Study on the molecular mechanism of the inherited factor X deficiency in three unrelated families / 中华检验医学杂志

Objective To identify the clinical features, the molecular diagnosis and the molecular mechanism of three unrelated factor X deficiency families. Methods Three probands were male and the diagnosis was validated by coagulant parameters. The F X coagulation activity ( F X∶ C ) and antigen (FX∶ Ag) were tested by clotting test and ELISA method. The cross-corrected test was used to rule out the inhibitor of FX in plasma. Thrombin generation test was evaluated. The antigen and the molecule weight of the FX in plasma were measured with western blotting. Gene mutations were analyzed in the probands and their family members with PCR and DNA sequencing. FX expression plasmids were constructed and transientby being transfected into 293T cells. FX: C and FX: Ag of the expression products were tested. Results APTT and PT in proband 1 were obviously prolonged, 113.4 s and 62.3 s, respectively. And there was no inhibitor in plasma. The thrombin generation was lower compared to normal reference. APTT and PT in proband 2 were 56. 5 s and 28.7 s. There was no inhibitor in the plasma. The thrombin generation was 1 101.5 nmol · min. APTT and PT in proband 3 were 117.3 s and 44. 3 s. The thrombin generation was 782.5 nmol · min. FX∶ C and FX∶ Ag in proband 1 were 1.4% and 3.6%, with a homozygous mutation in FX gene (Ser425→Pro). In vitro expression of the mutation showed a normal synthesis in the cell but secretion dysfuntion. In proband 2 F X: C and F X: Ag were 2. 2% and 5. 5%, with two heterozygous mutations in FX gene (Ala-29→Pro and Phe324→Leu). The Ala-29 → Pro mutation led to significantly reduced expressions of FX in both cell lysate and cell culture supernatants compared to wild-type plasmid,(41.32 ±5.21 )% and(6. 30 ± 1.84)% respectively. However Phe324→Leu mutation almost did not affect the FX synthesis. FX: C and FX: Ag in proband 3 were 2. 2% and 35%, with two heterozygous mutations in FX gene( Ala235→Thr and Arg347→Cys). The expressions of these two mutant FX proteins in cell lysate were similar to those of wild-type but obviously lower in the supernatant. Conclusions Five mutations of F X gene are found in this study. These mutations (Ser425Pro, Phe324Leu, Ala235Thr and Arg347Cys)can not affect F X protein synthesis. However Ala-29Pro mutation can reduce F X protein synthesis and cause secretion dysfunction.

A Case Report of Palatoplasty in a Patient with Clotting Factor X Deficiency

PURPOSE: Clotting factor X deficiency is one of the least common coagulation disorders. The authors describe a case of cleft palate in a patient with a congenital clotting factor X deficiency. METHODS: In pediatric patients with a cleft palate, the coagulation problem is more worrisome, because they are more sensitive to blood than adults, and because postoperative bleeding can cause blood ingestion with subsequent vomiting, aspiration, and airway obstruction. To prevent hemorrhagic complications in the described case, fresh frozen plasma (FFP) was administered every 24 hours from the day before surgery to the second postoperative day. RESULTS: Good hemostasis, normal healing, and no complications was shown postoperatively. CONCLUSION: The replacement of fresh frozen plasma was useful in the case of congenital clotting factor deficiency for bleeding prophylaxis in cleft palate operation.

A Case of Primary Amyloidosis with Nephrotic Syndrome and Factor X Deficiency / 대한신장학회지

We report a case of nephrotic syndrome and factor X deficiency secondary to primary amyloidosis. A 58-year-old man was referred to our hospital for evaluation of nephrotic syndrome and bleeding tendency. He was confirmed to have primary amyloidosis by renal biopsy, immunofixation electrophoresis and bone marrow findings. His bleeding tendency was due to prothrombin time prolongation caused by isolated factor X deficiency. If any patient with nephrotic syndrome has bleeding tendency due to coagulation abnormalities, that patient should be considered to have factor X deficiency secondary to primary amyloidosis.