Fibrinopeptide

Last updated
Fibrinopeptide A
Fibrinopeptide A.svg
Names
IUPAC name
(4S)-4-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-[[2-[[(2S)-3-carboxy-1-[[(2S)-1-[[1-[[(2S)-1-[[(2S)-4-carboxy-1-[[2-[[2-[[2-[[(2S)-1-[[(1S)-1-carboxy-4-(diaminomethylideneamino)butyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid
Other names
Fibrinopeptide A; Fibrinopeptide A (human); FpA; FPA
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C63H97N19O26/c1-29(2)19-37(57(102)73-32(6)53(98)76-35(15-17-48(91)92)55(100)70-24-43(85)68-23-42(84)69-25-46(88)82-51(30(3)4)61(106)77-36(62(107)108)13-10-18-67-63(65)66)79-58(103)38(20-33-11-8-7-9-12-33)80-59(104)39(21-49(93)94)75-45(87)27-71-54(99)34(14-16-47(89)90)74-44(86)26-72-56(101)41(28-83)81-60(105)40(22-50(95)96)78-52(97)31(5)64/h7-9,11-12,29-32,34-41,51,83H,10,13-28,64H2,1-6H3,(H,68,85)(H,69,84)(H,70,100)(H,71,99)(H,72,101)(H,73,102)(H,74,86)(H,75,87)(H,76,98)(H,77,106)(H,78,97)(H,79,103)(H,80,104)(H,81,105)(H,82,88)(H,89,90)(H,91,92)(H,93,94)(H,95,96)(H,107,108)(H4,65,66,67)/t31-,32-,34-,35-,36-,37?,38-,39-,40-,41-,51-/m0/s1
    Key: JWICNZAGYSIBAR-LEEGLKINSA-N
  • C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NC(CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N
Properties
C63H97N19O26
Molar mass 1536.57 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Fibrinopeptide B
Fibrinopeptide B.svg
Names
IUPAC name
(4S)-4-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-3-methyl-2-[[2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]acetyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]amino]-4-carboxybutanoyl]amino]-5-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid
Other names
Fibrinopeptide B; Fibrinopeptide B (human); FpB; FPB
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C66H93N19O25/c1-31(2)53(85-49(91)29-73-55(99)35-16-19-47(89)75-35)64(108)83-42(26-46(68)88)61(105)82-43(27-52(96)97)62(106)81-41(25-45(67)87)60(104)78-37(18-21-51(94)95)57(101)77-36(17-20-50(92)93)56(100)72-28-48(90)76-39(23-33-11-6-4-7-12-33)58(102)80-40(24-34-13-8-5-9-14-34)59(103)84-44(30-86)63(107)74-32(3)54(98)79-38(65(109)110)15-10-22-71-66(69)70/h4-9,11-14,31-32,35-44,53,86H,10,15-30H2,1-3H3,(H2,67,87)(H2,68,88)(H,72,100)(H,73,99)(H,74,107)(H,75,89)(H,76,90)(H,77,101)(H,78,104)(H,79,98)(H,80,102)(H,81,106)(H,82,105)(H,83,108)(H,84,103)(H,85,91)(H,92,93)(H,94,95)(H,96,97)(H,109,110)(H4,69,70,71)/t32-,35-,36-,37-,38-,39-,40-,41-,42-,43-,44-,53-/m0/s1
    Key: MYRIFIVQGRMHRF-OECXYHNASA-N
  • C[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@@H]3CCC(=O)N3
Properties
C66H93N19O25
Molar mass 1552.569 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

The fibrinopeptides, fibrinopeptide A (FpA) and fibrinopeptide B (FpB), are peptides which are located in the central region of the fibrous glycoprotein fibrinogen (factor I) and are cleaved by the enzyme thrombin (factor IIa) to convert fibrinogen into covalently-linked fibrin (factor IA) monomers. [1] [2] The N-terminal FpA is cleaved from the Aα chains of fibrinogen and FpB from the Bβ chains of fibrinogen, with FpA released before FpB. [3] [4] Subsequent to their formation, fibrin monomers are converted to cross-linked fibrin polymers by the action of thrombin-activated factor XIII (fibrin stabilizing factor), and these fibrin polymers form the backbone of a thrombus (blood clot). [2] Hence, the fibrinopeptides are sensitive markers of fibrinogenesis (fibrin generation), thrombin activity, and coagulation. [5] [6] [7] [8]

FpA is a 16-amino acid peptide. [8] The half-life of FpA is very short at approximately 3 to 5 minutes. [5] [8] Hence, FpA levels provide a relatively transient measure of coagulation activation. [8]

Levels of FpA increase with age. [5] FpA levels also gradually increase throughout pregnancy. [9] [10] Likewise, FpA levels have been reported to increase with estrogen therapy, including with combined birth control pills and menopausal hormone therapy, although research on FpA levels with these therapies appears to be relatively limited. [11] [12] [13] [7]

Related Research Articles

<span class="mw-page-title-main">Disseminated intravascular coagulation</span> Medical condition

Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts of the body. As clotting factors and platelets are used up, bleeding may occur. This may include blood in the urine, blood in the stool, or bleeding into the skin. Complications may include organ failure.

<span class="mw-page-title-main">Fibrinogen</span> Soluble protein complex in blood plasma and involved in clot formation

Fibrinogen is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clot. Fibrin clots function primarily to occlude blood vessels to stop bleeding. Fibrin also binds and reduces the activity of thrombin. This activity, sometimes referred to as antithrombin I, limits clotting. Fibrin also mediates blood platelet and endothelial cell spreading, tissue fibroblast proliferation, capillary tube formation, and angiogenesis and thereby promotes revascularization and wound healing.

<span class="mw-page-title-main">Thrombin</span> Enzyme involved in blood coagulation in humans

Thrombin is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the clotting process. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions.

<span class="mw-page-title-main">Partial thromboplastin time</span> Test for coagulation of blood

The partial thromboplastin time (PTT), also known as the activated partial thromboplastin time, is a blood test that characterizes coagulation of the blood. A historical name for this measure is the kaolin-cephalin clotting time (KCCT), reflecting kaolin and cephalin as materials historically used in the test. Apart from detecting abnormalities in blood clotting, partial thromboplastin time is also used to monitor the treatment effect of heparin, a widely prescribed drug that reduces blood's tendency to clot.

<span class="mw-page-title-main">Thrombophilia</span> Abnormality of blood coagulation

Thrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis. Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes. A significant proportion of the population has a detectable thrombophilic abnormality, but most of these develop thrombosis only in the presence of an additional risk factor.

<span class="mw-page-title-main">Activated protein C resistance</span> Medical condition

Activated protein C resistance (APCR) is a hypercoagulability characterized by a lack of a response to activated protein C (APC), which normally helps prevent blood from clotting excessively. This results in an increased risk of venous thrombosis, which resulting in medical conditions such as deep vein thrombosis and pulmonary embolism. The most common cause of hereditary APC resistance is factor V Leiden mutation.

Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation.

<span class="mw-page-title-main">Coagulation factor XIII, A1 polypeptide</span>

Coagulation factor XIII A chain is a protein that in humans is encoded by the F13A1 gene.

<span class="mw-page-title-main">Fibrin glue</span>

Fibrin glue is a surgical formulation used to create a fibrin clot for hemostasis, cartilage repair surgeries or wound healing. It contains separately packaged human fibrinogen and human thrombin.

Sticky platelet syndrome is a term used by some to describe a disorder of platelet function. It was first described by Mammen in 1983. It is inherited in an autosomal dominant pattern. It has not been associated with a specific gene, and it is not recognized as an entity in OMIM.

Blood clotting tests are the tests used for diagnostics of the hemostasis system. Coagulometer is the medical laboratory analyzer used for testing of the hemostasis system. Modern coagulometers realize different methods of activation and observation of development of blood clots in blood or in blood plasma.

Thrombin–antithrombin complex (TAT) is a protein complex of thrombin and antithrombin. It is a marker of net activation of coagulation.

Prothrombin fragment 1+2 (F1+2), also written as prothrombin fragment 1.2 (F1.2), is a polypeptide fragment of prothrombin generated by the in vivo cleavage of prothrombin into thrombin by the enzyme prothrombinase. It is released from the N-terminus of prothrombin. F1+2 is a marker of thrombin generation and hence of coagulation activation. It is considered the best marker of in vivo thrombin generation.

The calibrated automated thrombogram is a thrombin generation assay (TGA) and global coagulation assay (GCA) which can be used as a coagulation test to assess thrombotic risk. It is the most widely used TGA. The CAT is a semi-automated test performed in a 96-well plate and requires specialized technologists to be performed. As a result, it has seen low implementation in routine laboratories and has been more limited to research settings. Lack of standardization with the CAT has also led to difficulties in study-to-study comparisons in research. However, efforts have recently been made towards standardization of the assay. An example of a specific commercial CAT is the Thrombinoscope by Thrombinoscope BV.

The activated protein C resistance (APCR) test is a coagulation test used in the evaluation and diagnosis of activated protein C (APC) resistance, a form of hypercoagulability. Hereditary APC resistance is usually caused by the factor V Leiden mutation, whereas acquired APC resistance has been linked to antiphospholipid antibodies, pregnancy, and estrogen therapy. APC resistance can be measured using either an activated partial thromboplastin time (aPTT)-based test or an endogenous thrombin potential (ETP)-based test.

Plasmin-α2-antiplasmin complex (PAP) is a 1:1 irreversibly formed inactive complex of the enzyme plasmin and its inhibitor α2-antiplasmin. It is a marker of the activity of the fibrinolytic system and a marker of net activation of fibrinolysis.

The ST Genesia is a fully automated commercial analyzer system for performing thrombin generation assays (TGAs) and hence for coagulation testing. It was developed by Diagnostica Stago and was introduced by the company in 2018.

Fibrin monomers are monomers of fibrin which are formed by the cleavage of fibrinogen by thrombin. Levels of fibrin monomers in can be measured using blood tests and can serve as a marker of in vivo fibrinogenesis and coagulation activation. They may be useful in the evaluation hypercoagulability.

The overall hemostatic potential (OHP) test is a global coagulation assay which can be used to measure coagulation. The OHP assay measures total fibrin generation in the presence of thrombin or tissue factor and tissue plasminogen activator (t-PA). It generates a fibrin time curve through the use of optical density measurement. This curve represents the balance between fibrin formation induced by thrombin or tissue factor and fibrinolysis induced by t-PA. The assay provides three parameters: overall coagulation potential (OCP), overall hemostatic potential (OHP), and overall fibrinolytic potential (OFP). OHP is the main parameter, while OCP and OFP are supplementary parameters to assess coagulation and fibrinolysis. One further parameter, clot lysis time (CLT), can also be determined. The OHP assay measures the integrated effect of procoagulant, anticoagulant, and fibrinolytic factors.

Coagulation activation markers are biomarkers of net activation of coagulation and fibrinolysis. Examples include prothrombin fragment 1+2 (F1+2), thrombin–antithrombin complex (TAT), fibrinopeptide A (FpA), fibrin monomers (FMs), plasmin-α2-antiplasmin complex (PAP), activated protein C–protein C inhibitor (APC-PCI), and D-dimer (DD). These compounds are markers of thrombin generation, fibrin generation, and fibrinolysis. Coagulation activation markers, particularly D-dimer, are useful in the diagnosis of acute venous thromboembolism. They may also be useful in the assessment of hypercoagulability and venous thromboembolism risk.

References

  1. ↑ Weisel JW (2005). "Fibrinogen and fibrin". Adv Protein Chem. Advances in Protein Chemistry. 70: 247–99. doi:10.1016/S0065-3233(05)70008-5. ISBN   9780120342709. PMID   15837518.
  2. 1 2 Gentry PA (November 2004). "Comparative aspects of blood coagulation". Vet J. 168 (3): 238–51. doi:10.1016/j.tvjl.2003.09.013. PMID   15501141.
  3. ↑ Wolberg AS (September 2012). "Determinants of fibrin formation, structure, and function". Curr Opin Hematol. 19 (5): 349–56. doi:10.1097/MOH.0b013e32835673c2. PMID   22759629. S2CID   11358104.
  4. ↑ O'Riordan, Máiread N; Higgins, John R (June 2003). "Haemostasis in normal and abnormal pregnancy". Best Practice & Research Clinical Obstetrics & Gynaecology. 17 (3): 385–396. doi:10.1016/S1521-6934(03)00019-1. ISSN   1521-6934. PMID   12787533.
  5. 1 2 3 Mannucci PM (October 1994). "Mechanisms, markers and management of coagulation activation". Br Med Bull. 50 (4): 851–70. doi:10.1093/oxfordjournals.bmb.a072930. PMID   7804735.
  6. ↑ Vincent Marks; Thomas Cantor; Dusan Mesko; Rudolf Pullmann; Gabriela Nosalova (6 December 2012). Differential Diagnosis by Laboratory Medicine: A Quick Reference for Physicians. Springer Science & Business Media. pp. 443–. ISBN   978-3-642-55600-5. OCLC   1262382180.
  7. 1 2 Farris M, Bastianelli C, Rosato E, Brosens I, Benagiano G (October 2017). "Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis". Expert Rev Clin Pharmacol. 10 (10): 1129–1144. doi:10.1080/17512433.2017.1356718. PMID   28712325. S2CID   205931204.
  8. 1 2 3 4 Merlini PA, Ardissino D (1995). "Laboratory Measurement of Thrombin Activity--What Every Clinician Scientist Needs to Know". J Thromb Thrombolysis. 2 (2): 85–92. doi:10.1007/BF01064374. PMID   10608009. S2CID   28203940.
  9. ↑ Hellgren M (April 2003). "Hemostasis during normal pregnancy and puerperium". Semin Thromb Hemost. 29 (2): 125–30. doi:10.1055/s-2003-38897. PMID   12709915.
  10. ↑ Koltsova, Ekaterina; Balandina, Anna; Serebriyskiy, Ilya; Vuimo, Tatiana; Panteleev, Mikhail; Ataullakhanov, Fazoil (21 September 2016). "Classic and Global Hemostasis Testing in Pregnancy and during Pregnancy Complications". Seminars in Thrombosis and Hemostasis. 42 (7): 696–716. doi:10.1055/s-0036-1592303. eISSN   1098-9064. ISSN   0094-6176. PMID   27652600. S2CID   19571354.
  11. ↑ Douxfils J, Morimont L, Bouvy C (November 2020). "Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk". Semin Thromb Hemost. 46 (8): 872–886. doi:10.1055/s-0040-1714140. PMID   33080636. S2CID   224821517.
  12. ↑ Canonico M (July 2014). "Hormone therapy and hemostasis among postmenopausal women: a review" (PDF). Menopause. 21 (7): 753–62. doi:10.1097/GME.0000000000000296. PMID   24937030. S2CID   20851353.
  13. ↑ Baker L, Meldrum KK, Wang M, Sankula R, Vanam R, Raiesdana A, Tsai B, Hile K, Brown JW, Meldrum DR (December 2003). "The role of estrogen in cardiovascular disease". J Surg Res. 115 (2): 325–44. doi:10.1016/s0022-4804(03)00215-4. PMID   14697301.
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