Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Praha 2, Czech Republic.
J Thromb Thrombolysis. 2010 Oct;30(3):311-8. doi: 10.1007/s11239-010-0505-1.
Hereditary dysfibrinogenemia is a rare disorder wherein an inherited abnormality in fibrinogen structure may result in defective fibrin function and/or structure. Congenital hypofibrinogenemia is a rare autosomal bleeding disorder, either recessive or dominant, characterized by a low fibrinogen plasma level. A 28-year-old asymptomatic woman (fibrinogen Rokycany) and a 54-year-old man with thrombosis and pulmonary embolism (fibrinogen Znojmo) were investigated for a suspected fibrinogen mutation after abnormal coagulation tests results were obtained. DNA sequencing showed the heterozygous point mutation Bβ Asn351Lys in fibrinogen Rokycany and the heterozygous point mutation Bβ Arg237Ser in fibrinogen Znojmo, respectively. The kinetics of fibrinopeptide release was found to be normal in both cases. Fibrinolysis was impaired in the Znojmo variant. The average fibril diameters of Znojmo fibrin was slightly increased, but not differing significantly from normal; formed by less fibrils with abrupt fibril terminations. Rheological studies revealed a softer clot. Rokycany fibrin was formed by significantly narrower fibrils than normal fibrin; and the clot was denser than the control clot. Rheological studies revealed a stiffer clot. Impaired fibrinolysis and abnormal clot morphology may be the cause of thrombotic episodes in the patient with Znojmo mutation. New cases of hypofibrinogenemia and dysfibrinogenemia, found by routine coagulation testing, were genetically identified as a novel fibrinogen variants Bβ Asn351Lys (fibrinogen Rokycany) and Bβ Arg237Ser (fibrinogen Znojmo), respectively.
遗传性纤维蛋白原血症是一种罕见的疾病，其纤维蛋白原结构的遗传异常可能导致纤维蛋白功能和/或结构缺陷。先天性低纤维蛋白原血症是一种罕见的常染色体出血性疾病，为隐性或显性遗传，其特征是纤维蛋白原血浆水平低。一名 28 岁无症状女性（纤维蛋白原罗基察尼）和一名 54 岁有血栓和肺栓塞的男性（纤维蛋白原兹诺伊莫），在凝血检测异常结果后，被怀疑存在纤维蛋白原突变。DNA 测序显示纤维蛋白原罗基察尼存在杂合点突变 Bβ Asn351Lys，纤维蛋白原兹诺伊莫存在杂合点突变 Bβ Arg237Ser。两种情况下纤维蛋白肽释放动力学均正常。兹诺伊莫变体的纤维蛋白溶解受损。Znojmo 纤维蛋白的平均纤维直径略有增加，但与正常纤维无显著差异；形成的纤维较少，纤维末端突然终止。流变学研究显示凝块较软。罗基察尼纤维蛋白形成的纤维比正常纤维明显狭窄；并且凝块比对照凝块更密集。流变学研究显示凝块较硬。纤维蛋白溶解受损和异常的凝块形态可能是 Znojmo 突变患者发生血栓形成的原因。通过常规凝血检测发现的新的低纤维蛋白原血症和纤维蛋白原血症病例，通过基因鉴定分别为新型纤维蛋白原变体 Bβ Asn351Lys（纤维蛋白原罗基察尼）和 Bβ Arg237Ser（纤维蛋白原兹诺伊莫）。
