Congenital prothrombin deficiency.
Prothrombin deficiency is among the rarest inherited coagulation disorders, with a prevalence of approximately 1:2,000,000. Two main phenotypes can be distinguished: (1) hypoprothrombinemia (type I deficiency), characterized by concomitantly low levels of activity and antigen; and (2) dysprothrombinemia (type II deficiency), characterized by the normal or near-normal synthesis of a dysfunctional protein. In some cases, hypoprothrombinemia associated with dysprothrombinemia was also described in compound heterozygous defects. No living patient with undetectable plasma prothrombin has been reported to date. Prothrombin is encoded by a gene of approximately 21 kb located on chromosome 11 and containing 14 exons. Forty different mutations have been identified and characterized in prothrombin deficiency. Many of them surround the catalytic site, whereas another "hot spot" is localized in the recognition domain called anion binding exosite I, also called fibrinogen recognition site. Recently, mutations were identified also in the Na (+)-binding loop and in the light A-chain of thrombin. Most hypoprothrombinemia-associated mutations are missense, but there are also nonsense mutations leading to stop codons and one single nucleotide deletion. Finally, the main aspects of clinical manifestations and therapy of congenital prothrombin deficiency are presented and discussed.
Lancellotti
Stefano
S
Haemostasis Research Center, Department of Internal Medicine, Catholic University School of Medicine, 00168 Rome, Italy.
De Cristofaro
Raimondo
R
D000595:Amino Acid Sequence; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D019411:Clinical Laboratory Techniques; D010450:Endopeptidases; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006579:Heterozygote; D006801:Humans; D007020:Hypoprothrombinemias / Q000235:genetics* / Q000628:therapy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011300:Preoperative Care / Q000379:methods; D011516:Prothrombin / Q000235:genetics*; D013917:Thrombin / Q000235:genetics / Q000378:metabolism; D014757:Viper Venoms
D000933:Antifibrinolytic Agents; D001779:Blood Coagulation Factors; D014757:Viper Venoms; C025667:prothrombin complex concentrates; D011516:Prothrombin; D010450:Endopeptidases; D013917:Thrombin; C020097:ecarin