Thrombophilia natural history, complications and prognosis: Difference between revisions
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==Natural History== | ==Natural History== | ||
*If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and [[Prothrombin G20210A]] is low (<0.06%).<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[ | *If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and [[Prothrombin G20210A]] is low (<0.06%).<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[oral contraceptive]]s. | ||
*In patients on oral anticoagulant therapy for venous thromboembolism, the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref> | *In patients on oral anticoagulant therapy for venous thromboembolism, the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref> | ||
*Inherited thrombophilia from [[Factor V Leiden]] and [[Prothrombin G20210A]] did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref> | *Inherited thrombophilia from [[Factor V Leiden]] and [[Prothrombin G20210A]] did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref> | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Asiri Ediriwickrema, M.D., M.H.S. [2]
Overview
The annual thrombotic risks are variable and depend on the underlying thrombophilia.[1]
Natural History
- If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with Factor V Leiden and Prothrombin G20210A is low (<0.06%).[2] The risk is approximately equivalent to treatment with oral contraceptives.
- In patients on oral anticoagulant therapy for venous thromboembolism, the annual incidence of significant bleeds is approximately 2-3%.[3]
- Inherited thrombophilia from Factor V Leiden and Prothrombin G20210A did not predict for recurrent thrombosis.[4][5]
- In untreated patients with protein C, protein S, and antithrombin deficiencies, there is an increased risk for recurrent thrombosis.[4][6]
- Oral contraceptives, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.[7]
- Certain high risk thrombophilias require indefinite anticoagulation.
Complications
- The primary complication of thrombophilia is the development of blood clots
- Common complications of thrombophilia include deep vein thrombosis and pulmonary embolism
The risk of future thrombosis in patients with thrombophilia:
| Thrombophilic state | Thrombotic risk[2] |
|---|---|
| Trauma/General surgery | Modest |
| Age > 60 | Modest |
| Immobilization | Modest |
| Pregnancy | Modest |
| Hormone therapies | Modest |
| Factor V Leiden heterozygosity | Modest |
| Prothrombin mutation | Modest |
| Homocysteinemia | Modest |
| Increased factor VIII levels | Modest |
| Increased factor IX levels | Modest |
| Increased factor XI levels | Modest |
| Protein C and S deficiency | Intermediate |
| Dysfibrogenemia | Intermediate |
| Malignancy | High |
| APLS/Lupus anticoagulant | High |
| Myeloproliferative disorders/hyperviscosity | High |
| PNH | High |
| Orthopedic surgery | High |
| Antithrombin deficiency | High |
| Factor V Leiden homozygosity | High |
The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with thrombophilia:
| Thrombophilic state | Annual Incidence (%) | Relative Risk |
|---|---|---|
| Normal | 0.008 | 1 |
| Factor V Leiden heterozygous | 0.06 | 3-10 |
| Factor V Leiden homozygous | 0.5-1 | 80 |
| Prothrombin G20210A | 0.02 | 1-5 |
| Oral contraceptive (OCP) | 0.03 | 4 |
| OCP and factor V leiden heterozygous | 0.3 | 35 |
| OCP and factor V leiden homozygous | 100 | |
| OCP and prothrombin G20210A | 16 | |
| OCP and protein C/S, or antithrombin III deficiency | 9.7 | |
| Pregnancy | 7 | |
| Pregnancy and factor V leiden heterozygous | 35 | |
| Cancer | 5 | |
| History of venous thrombosis | 50 |
Data were extracted from multiple sources.[1][2][7]
Prognosis
The prognosis depends on the underlying thrombophilia as each form has a different associated thrombotic risk. Patients who develop multiple or atypical clots, arterial thrombosis, or life-threatening thrombosis have worse prognosis.
Thrombophilias generally associated with worse prognosis include:
- Antiphospholipid Syndrome
- Paroxysmal nocturnal hemoglobinuria
- Antithrombin III deficiency
- Factor V Leiden homozygosity
Certain thrombophilic conditions are high risk and require consideration for lifelong anticoagulation. In these cases, expert consultation is recommended.
| Possible indications for lifelong/prophylactic anticoagulation |
|---|
| Antiphospholipid syndrome |
| Paroxysmal nocturnal hemoglobinuria |
| Recurrent thrombosis regardless of underlying thrombophilia |
| History of life-threatening thrombosis or atypical locations |
| Malignancy with history of thrombosis |
References
- ↑ 1.0 1.1 Bauer KA (2001). "The thrombophilias: well-defined risk factors with uncertain therapeutic implications". Ann Intern Med. 135 (5): 367–73. PMID 11529700.
- ↑ 2.0 2.1 2.2 Bates SM, Ginsberg JS (2004). "Clinical practice. Treatment of deep-vein thrombosis". N Engl J Med. 351 (3): 268–77. doi:10.1056/NEJMcp031676. PMID 15254285.
- ↑ Linkins LA, Choi PT, Douketis JD (2003). "Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis". Ann Intern Med. 139 (11): 893–900. PMID 14644891.
- ↑ 4.0 4.1 Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR (2005). "Thrombophilia, clinical factors, and recurrent venous thrombotic events". JAMA. 293 (19): 2352–61. doi:10.1001/jama.293.19.2352. PMID 15900005. Review in: Evid Based Med. 2006 Apr;11(2):59
- ↑ Baglin T, Luddington R, Brown K, Baglin C (2003). "Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study". Lancet. 362 (9383): 523–6. doi:10.1016/S0140-6736(03)14111-6. PMID 12932383.
- ↑ De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A; et al. (2006). "The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S." Haematologica. 91 (5): 695–8. PMID 16670075.
- ↑ 7.0 7.1 Dalen JE (2008). "Should patients with venous thromboembolism be screened for thrombophilia?". Am J Med. 121 (6): 458–63. doi:10.1016/j.amjmed.2007.10.042. PMID 18501222.