Thrombophilia natural history, complications and prognosis: Difference between revisions
Jump to navigation
Jump to search
mNo edit summary |
|||
| (21 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
__NOTOC__ | __NOTOC__ | ||
{{Thrombophilia}} | {{Thrombophilia}} | ||
{{CMG}}; {{AE}} {{asiri}} | {{CMG}}; {{AE}} {{asiri}} {{JK}} | ||
==Overview== | ==Overview== | ||
| Line 7: | Line 7: | ||
==Natural History== | ==Natural History== | ||
* | *[[Factor V Leiden]] and [[Prothrombin G20210A]]: If left untreated, the annual incidence of incident thrombosis in asymptomatic patients is low (<0.06%). However, the occurrence of recurrent thrombosis can not be predicted in such inherited thrombophilias. <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><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> | ||
*[[Protein_C|Protein C]], [[Protein_S|Protein S]], and [[Antithrombin]] deficiencies: These conditions carries an increased risk for recurrent thrombosis in untreated patients. <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="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref> | |||
*[[Oral contraceptives]], [[hormone replacement therapy]], and [[pregnancy]] can significantly increase thrombotic risk in patients with underlying thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref> | |||
* | *Certain high risk thrombophilias require indefinite [[anticoagulant|anticoagulation]]. However, such patients on preventive oral anticoagulant therapy for venous thromboembolism still carries the annual incidence of significant bleeds of ~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> | ||
*[[Oral contraceptives]], [[hormone replacement therapy]], and [[pregnancy]] can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref> | |||
*Certain high risk thrombophilias require indefinite [[anticoagulant|anticoagulation]]. | |||
==Complications== | ==Complications== | ||
*The primary complication of thrombophilia is the development of [[Thrombus|blood clots]] | *The primary complication of thrombophilia is the development of [[Thrombus|blood clots]], also known as '''thrombus formation'''. | ||
* | *The most common complications of thrombophilia are as follows: <ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref><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><ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref> | ||
**[[Deep vein thrombosis]] | |||
**[[Pulmonary embolism]] | |||
** Postthrombotic syndrome (PTS) with chronic venous ulceration (CVU) <ref name="pmid23762560">{{cite journal| author=Rabinovich A, Kahn SR| title=Association between Thrombophilia and the Post-Thrombotic Syndrome. | journal=Int J Vasc Med | year= 2013 | volume= 2013 | issue= | pages= 643036 | pmid=23762560 | doi=10.1155/2013/643036 | pmc=3665186 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23762560 }} </ref> | |||
'''Table 1: The risk of future thrombosis in patients with thrombophilia:''' | |||
{| class="wikitable" | {| class="wikitable" | ||
|- | |- | ||
| | ! style="font-weight: bold;" |Thrombotic risk<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> | ||
| | !! style="font-weight: bold;" |Thrombophilic state | ||
|- | |- | ||
| | | '''Modest''' || [[Trauma]]/[[General surgery]], [[Elderly|Age > 60]], [[Immobilization]], [[Pregnancy]], [[Hormone therapy|Hormone therapies]], [[Factor V Leiden]] heterozygosity, [[Prothrombin]] mutation, Homocysteinemia, Increased factor VIII levels, Increased factor IX levels, Increased factor XI levels | ||
| | |||
|- | |- | ||
| | | '''Intermediate''' || Protein C and S deficiency, Dysfibrogenemia | ||
| | |||
| | |||
|- | |- | ||
| '''High''' || [[Malignancy]], APLS/[[Lupus anticoagulant]], Myeloproliferative disorders/hyperviscosity, PNH, [[Orthopedic surgery]], [[Antithrombin deficiency]], Factor V Leiden homozygosity | |||
|} | |} | ||
'''The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with thrombophilia:''' | '''Table 2: The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with underlying thrombophilia:''' | ||
{| class="wikitable" | {| class="wikitable" | ||
! style="font-weight: bold;" | Thrombophilic state | ! style="font-weight: bold;" | Thrombophilic state | ||
| Line 111: | Line 59: | ||
| 4 | | 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]] | | [[Pregnancy]] | ||
| Line 131: | Line 79: | ||
| 7 | | 7 | ||
|- | |- | ||
| Pregnancy and factor V leiden heterozygous | |||
| | | | ||
| 35 | |||
|- | |- | ||
| [[Cancer]] | | [[Cancer]] | ||
| Line 143: | Line 91: | ||
| 50 | | 50 | ||
|} | |} | ||
==Prognosis== | ==Prognosis== | ||
The prognosis depends on the underlying thrombophilia as each | *The prognosis depends on the underlying thrombophilia as each disorder has a different associated thrombotic risk (Table 1 and 2). | ||
*Thrombophilias associated with the development of multiple or atypical clots, arterial thrombosis, or life-threatening thrombosis carries '''worse prognosis''' which are as follows: | |||
**[[Antiphospholipid Syndrome]] | |||
*[[Antiphospholipid Syndrome]] | **[[Paroxysmal nocturnal hemoglobinuria]] | ||
*[[Paroxysmal nocturnal hemoglobinuria]] | **[[Antithrombin III deficiency]] | ||
*[[Antithrombin III deficiency]] | **[[Factor V Leiden]] homozygosity | ||
*[[Factor V Leiden]] homozygosity | *High risk thrombophilic conditions require consideration for '''lifelong [[anticoagulation]]''' under the supervision of an expert consultant. | ||
**[[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== | ==References== | ||
Latest revision as of 20:14, 12 March 2021
|
Thrombophilia Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Thrombophilia natural history, complications and prognosis On the Web |
|
American Roentgen Ray Society Images of Thrombophilia natural history, complications and prognosis |
|
FDA on Thrombophilia natural history, complications and prognosis |
|
CDC on Thrombophilia natural history, complications and prognosis |
|
Thrombophilia natural history, complications and prognosis in the news |
|
Blogs on Thrombophilia natural history, complications and prognosis |
|
Risk calculators and risk factors for Thrombophilia natural history, complications and prognosis |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Asiri Ediriwickrema, M.D., M.H.S. [2] Jaspinder Kaur, MBBS[3]
Overview
The annual thrombotic risks are variable and depend on the underlying thrombophilia.[1]
Natural History
- Factor V Leiden and Prothrombin G20210A: If left untreated, the annual incidence of incident thrombosis in asymptomatic patients is low (<0.06%). However, the occurrence of recurrent thrombosis can not be predicted in such inherited thrombophilias. [2][3][4]
- Protein C, Protein S, and Antithrombin deficiencies: These conditions carries an increased risk for recurrent thrombosis in untreated patients. [3][5]
- Oral contraceptives, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with underlying thrombophilia.[6]
- Certain high risk thrombophilias require indefinite anticoagulation. However, such patients on preventive oral anticoagulant therapy for venous thromboembolism still carries the annual incidence of significant bleeds of ~2-3%.[7]
Complications
- The primary complication of thrombophilia is the development of blood clots, also known as thrombus formation.
- The most common complications of thrombophilia are as follows: [1][2][6]
- Deep vein thrombosis
- Pulmonary embolism
- Postthrombotic syndrome (PTS) with chronic venous ulceration (CVU) [8]
Table 1: The risk of future thrombosis in patients with thrombophilia:
| Thrombotic risk[2] | Thrombophilic state |
|---|---|
| Modest | Trauma/General surgery, Age > 60, Immobilization, Pregnancy, Hormone therapies, Factor V Leiden heterozygosity, Prothrombin mutation, Homocysteinemia, Increased factor VIII levels, Increased factor IX levels, Increased factor XI levels |
| Intermediate | Protein C and S deficiency, Dysfibrogenemia |
| High | Malignancy, APLS/Lupus anticoagulant, Myeloproliferative disorders/hyperviscosity, PNH, Orthopedic surgery, Antithrombin deficiency, Factor V Leiden homozygosity |
Table 2: The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with underlying 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 |
Prognosis
- The prognosis depends on the underlying thrombophilia as each disorder has a different associated thrombotic risk (Table 1 and 2).
- Thrombophilias associated with the development of multiple or atypical clots, arterial thrombosis, or life-threatening thrombosis carries worse prognosis which are as follows:
- High risk thrombophilic conditions require consideration for lifelong anticoagulation under the supervision of an expert consultant.
- 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.
- ↑ 3.0 3.1 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.
- ↑ 6.0 6.1 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.
- ↑ 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.
- ↑ Rabinovich A, Kahn SR (2013). "Association between Thrombophilia and the Post-Thrombotic Syndrome". Int J Vasc Med. 2013: 643036. doi:10.1155/2013/643036. PMC 3665186. PMID 23762560.