PlasmaThe Non-cellular Components of Blood
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
Various proteins belong to this group of globulins: α2-Macroglobulin. This is a protease inhibitor in plasma and is the major protein in the α2-globulin fraction (∼80%). It has inhibitory functions on plasma trypsin, chymotrypsin and plasmin. The primary function of α2-macroglobulin may be to inhibit proteases produced by infectious organisms.Prothrombin. Prothrombin is a clotting factor synthesized by the liver. About 60% of the extracellular pool of prothrombin is in the plasma and 40% in the extravascular space. It has a rapid turnover.Haptoglobin. This is a heterogeneous group of globulins that bind free Hb and transport it to the liver.Ceruloplasmin. Ceruloplasmin is a plasma protein that carries copper and is produced in the liver. It also functions as an oxidase enzyme and oxidizes ferrous to ferric ions before the binding of iron to transferrin. As an acute-phase protein, it may modulate inflammation by its free-radical scavenging properties.
Methods of nutritional assessment and surveillance
Geoffrey P. Webb in Nutrition, 2019
Vitamin K status is frequently assessed by functional tests of prothrombin levels in blood. Prothrombin is one of the several clotting factors whose synthesis in the liver depends upon vitamin K as an essential cofactor. Thus, in vitamin K deficiency, prothrombin levels fall and blood clotting is impaired. In order to measure the prothrombin time, excess calcium and tissue thromboplastin are added to fresh plasma that has been previously depleted of calcium to prevent clotting. The time taken for the plasma to clot under these conditions is dependent upon the amount of prothrombin present and thus upon the vitamin K status of the donor. Anti-coagulant drugs, like warfarin, work by blocking the effect of vitamin K. Prothrombin time is thus a useful way of monitoring vitamin K status and thus of regulating drug dosage during anti-coagulant therapy.
Current recommendations for the prevention of deep venous thrombosis
Peter Gloviczki, Michael C. Dalsing, Bo Eklöf, Fedor Lurie, Thomas W. Wakefield, Monika L. Gloviczki in Handbook of Venous and Lymphatic Disorders, 2017
Warfarin is an oral anticoagulant that acts by inhibiting the post-translational vitamin K-dependent carboxylation of glutamic acid residues of hepatically synthesized clotting factors and anticoagulant proteins.54 These include factors II, VII, IX, and X, and the anticoagulant proteins C and S. Carboxylation enables protein incorporation of calcium, which is necessary for proper folding and activation. In the absence of calcium, these proteins cannot become activated and functionality is lost. Therapeutic doses of warfarin decrease the total amount of the active form of each vitamin K-dependent clotting factor by approximately 30%–50%. A decrease in concentration of clotting factors is sequential and is related to the half-lives of the individual factors. The overall anticoagulant effect is generally seen between 24 and 48 hours after drug administration. However, the peak anticoagulant effect may be delayed by 72–96 hours. Regular monitoring of warfarin therapy is performed to improve both the safety and efficacy of this drug. The prothrombin time international normalized ratio (INR) is a clot-based assay that directly correlates with the clotting factor activity. Therapeutic warfarin for most indications is associated with INR values between 2 and 3.
Central retinal artery occlusion and subsequent amaurosis fugax in the contralateral eye associated with the G20210A prothrombin gene (F2) variant: a case report
Published in Ophthalmic Genetics, 2022
María Camila Sierra-Cote, Juliana Muñoz-Ortiz, Juan Sebastián Botero-Meneses, Carolina Saldarriaga-Santos, Natalia Camacho, William Rojas-Carabali, Alejandra de-la-Torre
Regarding the genetic component, one of the most common variants in the prothrombin gene (F2) is the G20210A. Prothrombin is a glycoprotein and precursor form of Factor II (thrombin), and it is essential for the final phase of clotting (5). It is encoded by the F2 gene located in the short arm of chromosome 11 (11p11.2). Variants in this gene, including polymorphisms and variants, may lead to thrombophilic disorders in many patients (6,7). Although the G20210A is an established risk factor for venous thrombosis, and it is debatable that this variant is a risk factor for arterial thromboembolism, some cases have been linked to myocardial infarction and cerebral arterial disease (8). In the case of ocular vessel occlusions, studies are scarce (9–12). This study aims to report the fourth case described in the literature of CRAO associated with prothrombin G20210A pathogenic variant and the first case with bilateral ocular findings (9–11), emphasizing the usefulness of OCT-A in reaching the diagnosis and establishing the specific and timely therapeutic measures.
Nutritional deficiency presenting as acute pain, fatigue and bruising in a college health clinic
Published in Journal of American College Health, 2022
Adam Pallant, Tanya Sullivan, Andrew Kaluzny
Examination on follow-up 10 days after initial presentation is notable for a young man who now appears extremely fatigued with visible pallor. He is unable to stand fully upright due to pain in his joints, and demonstrates persistent mild flexion at both knees secondary to this pain (Figure 1). Vitals: temperature of 99.3, orthostasis with a supine pulse of 116 and a standing pulse of 140. Blood pressure remains stable and weight is unchanged. Physical exam is significant for markedly increased breadth and intensity of broad ecchymoses across the medial portion of bilateral thighs (Figure 2), and significant petechial hemorrhage on the lower extremities (Figure 3). Hemoglobin has dropped to 9.5 g/dl, and a mild lymphopenia is noted at 0.9 × 109/l with remainder of the differential normal. The platelet count remains normal at the 261 × 109/l. Total bilirubin has increased to 2.3 mg/dl (direct bilirubin of 0.4 mg/dl) with an elevated LDH of 240 IU/L. Prothrombin time is mildly elevated to 13.6 seconds (9.5-12.5) within normal INR of 1.2. ALT, AST, TIBC, and ferritin are normal.
Association of venous thromboembolism and myocardial infarction with Factor V Leiden and Factor II gene mutations among Libyan patients
Published in Libyan Journal of Medicine, 2021
Abdulghani Msalati, Abdulla Bashein, Murad Ghrew, Ibtesam Khalil, Khaled Sedaa, Abushawashi Ali, Ahmed Zaid
Coagulation Factor V has a single point mutation at position 1691 in exon 10, replacing guanine with adenine (G1691A); it is called Factor V Leiden. This mutation leads to the replacement of the amino acid arginine (R) at codon 506 with the amino acid glutamine (Q), (R506Q). This mutation makes Factor V become resistant to cleavage by activated protein C (APC) [4]. The lack of FV inactivation by APC leads to a 5- to 10-fold increase in the likelihood of thrombus formation [5]. The gene for Factor II is located on chromosome 11p11-q12 [6]. Prothrombin is a vitamin K-dependent glycoprotein. It is synthesized in the liver as an inactive zymogen, and it is activated by Factor Xa to the serine protease thrombin. The prothrombin gene contains 14 exons and spans about 21 kb. It encodes a 622-residue prepropeptide with a molecular mass of about 70 kD [7]. The mature circulating protein has 579 residues. The active enzyme alpha thrombin is produced by several cleavage events of prothrombin protein. A point transition mutation G20,210A (rs1799963), which was found in the 3ʹ untranslated region of the prothrombin gene in 1996, was associated with higher plasma prothrombin levels and an increased risk of venous thrombosis. The G20210A mutation leads to increased prothrombin levels and thus to the activation of thrombin [8,9].
Related Knowledge Centers
- Enzyme
- Factor X
- Fibrin
- Fibrinogen
- Proteolysis
- Serine Protease
- Vitamin K
- Gene
- Factor V
- Prothrombinase