Detection of the Leu40Arg variant of the platelet glycoprotein IIb/IIIa receptor in subjects with thrombotic diseases (original) (raw)

Pathogenesis & Laboratory approach to Thrombophilia

Eastern Journal of Medicine, 2009

Abstract. Thrombophilia is a term used for any hypercoagulable state, either inherited or acquired. The former is considered after excluding acquired predisposing causes like trauma, immobility, Dirseminated inta vascular cuagulation, pregnancy and anitphospholipid syndrome etc. It frequently results from interplay of genetic and acquired factors. An individual’s risk for DVT would be determined by the combination of his or her baseline propensity for thrombosis and the magnitude of the acute insult. Inherited hypercoagulable states may be secondary to deficiency of natural clotting inhibitors or elevated procoagulants or increased fibrinolytic factors . Amongst these, activated protein C resistance, is the commonest underlying cause .Testing for thrombophilia is best performed in stages. Highest-yield assays (screening tests) should be performed first and, if positive, should be followed by appropriate confirmatory tests. Cornerstone of initial treatment is heparin, either unfract...

Laboratory Investigation of Thrombophilia: The Good, the Bad, and the Ugly

Seminars in Thrombosis and Hemostasis, 2009

Thrombophilia can be broadly defined as an increased tendency toward hypercoagulability and venous thrombosis. There are several defined risk factors for thrombosis, and these are generally distinguished as either acquired or congenital, although sometimes this distinction is blurred because of interrelationships. Congenital risk factors include deficiencies or defects in natural anticoagulants, such as antithrombin, Protein C and Protein S, and genetic polymorphisms such as prothrombin G20210A and cleavageresistant forms of factor V (in particular factor V Leiden), that lead to a condition commonly known as activated protein C resistance. Acquired risk factors include antiphospholipid antibodies, detected as lupus anticoagulants and/or anticardiolipin antibodies and/or anti-b-2-glycoprotein-I antibodies. High levels of clotting factors, dysfibrinogenemia, hyperhomocysteinemia, prolonged immobilization, increasing age, surgery, trauma, cancer, obesity, poor nutrition, pregnancy, oral contraceptives, and hormone replacement therapy comprise just some of the other risk factors. Each of these elements constitutes a component of increased risk, which is compounded when concomitant. There is ongoing debate regarding relative and compound risks, the value of laboratory screening, whom and when to screen for these markers, which tests and methodologies to use, and the form and duration of therapeutic management. The current article explores several important issues primarily from a scientific perspective and predominantly related to laboratory testing. Many of these issues appear to be simply overlooked by some clinicians managing patients with thromboses. In brief, although there is potential significance in testing for various thrombophilia-associated markers, this value is limited and greatly diminishes when inappropriately applied. The application of excessive or inappropriate thrombophilia testing is of particular concern, and the net effect of current worldwide testing trends is likely to be more detrimental than beneficial. In short, it is likely that current generalized testing is simply doing more harm than good, and thus that ordering practice requires scrutiny.

Prevalence of thrombophilia in asymptomatic individuals with a family history of thrombosis

Hippokratia, 2013

The present study investigates the prevalence of thrombophilia in individuals with first or/and second degree family history of thromboembolism. The study group consisted of 68 individuals with a first or second degree family history of venous or arterial thromboembolism, but without a personal history of thrombosis. The activity of ATIII, PC, PS, FVIII, FΧΙΙ and total homocysteine was measured on the ACL Advance coagulation analyzer. In addition, hemi-quantitative determination of CRP was performed to exclude an acute phase reaction. The existence of V-Leiden mutation was investigated by the modified pre-dilution method (1:5) with V-DEF. Prothrombin G20210A mutation was detected by the use of an in house PCR protocol. Family history was termed as follows: positive (thrombosis was reported in one parent and his/her family members) (group Α) or strongly positive (thrombosis was reported in both parents and their family members (group Β). Data analysis revealed decreased activity of A...

Guidance for the evaluation and treatment of hereditary and acquired thrombophilia

Journal of Thrombosis and Thrombolysis, 2016

Thrombophilias are hereditary and/or acquired conditions that predispose patients to thrombosis. Testing for thrombophilia is commonly performed in patients with venous thrombosis and their relatives; however such testing usually does not provide information that impacts management and may result in harm. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for thrombophilia testing in five clinical situations: following 1) provoked venous thromboembolism, 2) unprovoked venous thromboembolism; 3) in relatives of patients with thrombosis, 4) in female relatives of patients with thrombosis considering estrogen use; and 5) in female relatives of patients with thrombosis who are considering pregnancy. Additionally, guidance is provided regarding the timing of thrombophilia testing. The role of thrombophilia testing in arterial thrombosis and for evaluation of recurrent pregnancy loss is not addressed. Statements are based on existing guidelines and consensus expert opinion where guidelines are lacking. We recommend that thrombophilia testing not be performed in most situations. When performed, it should be used in a highly selective manner, and only in circumstances where the information obtained will influence a decision important to the patient, and outweigh the potential risks of testing. Testing should not be performed during acute thrombosis or during the initial (3-month) period of anticoagulation.

Thrombophilia and Other Conditions Associated with Acute Forms of Cardiovascular Disease

Cardiologia Croatica, 2015

Svjedoci smo sve češćih slučajeva akutnih koronarnih sindroma u mlađih bolesnika, odnosno u bolesnika u kojih ne nalazimo prisutne tipične preinačive ili nepreinačive čimbenike rizika. Većina studija defi nira mlađe pacijente kao osobe dobi do 45 godina. U takvih se bolesnika obično dijagnosticira akutni infarkt miokarda (AIM) s normalnim koronarnim arterijama, odnosno koronarne arterije ne pokazuju intraluminalne nepravilnosti (stroga defi nicija) ili arterije s manjim stupnjem stenoze, ali hemodinamski bez značenja (u većini slučajeva < 30% stenoza). Nedavno objavljena studija (APPROACH) utvrdila je učestalost akutnog infarkta miokarda s normalnim koronarnim arterijama u iznosu od 2,8% u bolesnika podvrgnutih koronarnoj angiografi ji kod AIM-a. Diferencijalna dijagnoza takvih akutnih koronarnih zbivanja uključuje miokarditis, stres miokardiopatije i sindrom baloniranja vrška lijeve klijetke. Ne postoji jedinstveno objašnjenje nastanka AIM-a s normalnim koronarnim arterijama, ali predloženo je nekoliko mogućih mehanizama: latentna ateroskleroza, vazospazam, tromboza i hiperkoagulabilno stanje, embolizacija i upala. Postoje stečeni i nasljedni sindrom trombofi lije. U ovom ćemo prikazu opisati povezanost između nasljednih oblika trombofl ije u koje ubrajamo mutaciju faktora V Leiden, mutacija gena za protrombin, manjak proteina C i proteina S, manjak antitrombina i mutacija gena za glikoprotein inhibitor plazminogen aktivatora-1 s akutnim oblicima srčanožilnih bolesti. SUMMaRY: We are witnessing increasingly frequent cases of acute coronary syndrome in younger patients, or in patients who did not present the typical risk factors. Most studies defi ne younger patients as persons under 45 years of age. Such patients are typically diagnosed with acute myocardial infarction (AMI) with normal coronary arteries, i.e. the coronary artery does not show intraluminal anomalies (strict defi nition) or with a smaller artery stenosis but hemodynamically insignifi cant (in most cases <30% stenosis). A recently published study (APPROACH) determined the prevalence of AMI with normal coronary arteries was 2.8% in patients who underwent coronary angiography for AMI. Differential diagnosis of such acute coronary events includes myocarditis, stress cardiomyopathy, and Takotsubo syndrome. There is no single explanation for the origin of AMI with normal coronary arteries, but a few possible mechanisms have been suggested: latent atherosclerosis, vasospasm, thrombosis and hypercoagulability, embolization, and infl ammation. We differentiate between acquired and inherited thrombophilia syndrome. In this report, we will describe a link between hereditary forms of trombophilia (a mutation of factor V Leiden, prothrombin gene mutation, defi ciency of protein C and protein S, antithrombin defi ciency, and mutations in the gene for glycoprotein plasminogen activator inhibitor-1) and acute forms of cardiovascular disease. KlJUČNe RIJeČI: trombofi lija, akutni koronarni sindrom, infarkt miokarda s urednim koronarnim arterijama.