Hereditary Plasma Protein Disorders
Genesio Murano, Rodger L. Bick in Basic Concepts of Hemostasis and Thrombosis, 2019
In most of these disorders the pathophysiology is poorly understood. There are a variety of different types of dysfibrogenemias, and varying characteristics are noted for each. Immunologic methods always reveal fibrinogen levels to be normal or increased. Various defects have been described for each particular type of dysfibrinogenemia and have included such findings as abnormal immunoelectrophoretic mobility, abnormal carbohydrate content, and slow release of fibrinopeptide A or B with thrombin. The most completely characterized dysfibrinogenemia is fibrinogen Detroit.35 In this instance, the amino acid serine is substituted for arginine in position 19 of the A α chain (Figure 4 in Chapter 3). This unique and laborious discovery represents the second disease state to be defined by a single amino acid substitution — the first, of course, being sickle cell anemia. Table 4 lists the congenital dysfibrinogenemias thus far described.
Thrombosis, heparin and laboratory monitoring of heparin therapy
John Edward Boland, David W. M. Muller in Interventional Cardiology and Cardiac Catheterisation, 2019
Following spontaneous or chemically induced lysis of a thrombus, thrombin may become exposed to circulating blood, leading to activation of platelets and coagulation factors and culminating in further thrombosis. The antithrombin activity of heparin is limited for three major reasons. First, residual thrombus contains thrombin bound to fibrin, which is poorly accessible to the heparin-ATIII complex and requires about 20 times more heparin for inactivation compared to unbound thrombin. Second, platelet-rich arterial thrombus releases large amounts of platelet factor 4, which inhibits heparin. Third, the fibrin II monomer, formed by the action of thrombin on fibrinogen, is also an inhibitor of heparin. Hirudin, a naturally occurring compound derived from leech saliva, has antithrombin properties and is at least 10 times smaller than the heparin-ATIII complex. It has no natural inhibitors. As such, it is more accessible to thrombin bound to fibrin, and may prove to have a clinically useful role in this situation.
Development of palliative medicine in the United Kingdom and Ireland
Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita in Textbook of Palliative Medicine and Supportive Care, 2015
Due to the risk of life-threatening thromboembolism formation, it is imperative to treat HIT as soon as it is diagnosed. The first step is to discontinue all exposure to heparin-containing products, including catheters coated with heparin. Aside from stopping heparin use, treatment with a direct thrombin inhibitor such as lepirudin, bivalirudin, or argatroban is necessary as there is an increased risk of developing thrombosis. When transitioning to warfarin, current recommendations are to start warfarin once the platelet count has plateaued above 150,000μL-1[22], and the transition should occur after the patient has been adequately anticoagulated [23]. Warfarin treatment is initiated in patients who are in need of longterm anticoagulation with a goal international normalized ratio (INR) of 2-3[24]. Situations that may require long-term anticoagulation include patients with a history of HIT and the sustained presence of antibodies [24] and those at risk of future thrombus formation. Platelet transfusion should be used in patients with HIT and severe thrombocytopenia, only when bleeding or during an invasive procedure with a high risk of bleeding [22].
Congenital prothrombin defects: they are not only associated with bleeding but also with thrombosis: a new classification is needed
Published in Hematology, 2018
Antonio Girolami, Silvia Ferrari, Elisabetta Cosi, Bruno Girolami, Anna Maria Lombardi
The Arg382His mutation does not belong to the classic group which involves Arg596Leu or Gln or Trp mutations. Due to the different site of the mutation, the condition has to be considered a dysprothrombinemia with both bleeding and thrombosis secondary to intensive replacement therapy even though a contributory effect of other factors cannot be excluded [18]. Thrombotic events, both arterial and venous, have been described in several coagulation factors deficiencies after or during replacement therapy [19–23].
New data on FII, FV, FIX and thrombomodulin defects: blood keeps clotting in normal and in peculiar ways
Published in Hematology, 2019
Antonio Girolami, Silvia Ferrari, Bruno Girolami, Maria Luigia Randi
All these prothrombin defects show a variable bleeding tendency but no thrombosis. It is interesting to note that all patients with dysprothrombinemia and thrombosis are heterozygotes for the mutation. This indirectly confirms the fact that homozygosis for ‘true’ prothrombin deficiency is very severe and sometimes incompatible with life [11,12].
Related Knowledge Centers
- Enzyme
- Factor X
- Fibrin
- Fibrinogen
- Proteolysis
- Serine Protease
- Vitamin K
- Gene
- Factor V
- Prothrombinase