Prevalence and Outcomes of Thrombophilia in Patients with Acute Pulmonary Embolism

Figures & data

Table 1 Main Clinical Features and Risk Factors of Acute PE by Thrombophilia

	Overall (n=227)	Non-Thrombophilia (n=119)	Thrombophilia* (n=108)	P value
Age (mean±SD)	50.6±16.9	55.4±18.1	45.2±13.9	0.001
Males	125 (55.1%)	60 (50.4%)	65 (60.2%)	0.14
Body mass index (n=148)	32.6±9.9	31.8±8.9	33.7±11.1	0.26
Location of Diagnosis
Emergency/ICU	155 (68.3%)	70 (58.8%)	85 (78.7%)	0.001 for all
In-hospital wards	57 (25.1%)	42 (35.3%)	15 (13.9%)
Outpatient presented at ED	15 (6.6%)	7 (5.9%)	8 (7.4%)
Frequency of admissions	1 (1–3)	1 (1–3)	1 (1–3)	0.09
Clinical Presentation
Dyspnea (n=187)	147 (78.6%)	73 (72.3%)	74 (86.0%)	0.02
Chest pain (n=183)	114 (62.3%)	53 (53.5%)	61 (72.6%)	0.008
Shortness of breath (n=220)	51 (23.2%)	28 (25.0%)	23 (21.3%)	0.51
Syncope (n=165)	23 (12.9%)	12 (12.4%)	11 (13.6%)	0.81
Cardiogenic shock	7 (4.2%)	5 (5.4%)	2 (2.7%)	0.39
Number of CT scans	1 (1–11)	1 (1–11)	1 (1–8)	0.17
Comorbidities/Risk Factors
Hypertension	78 (37.9%)	46 (40.7%)	32 (34.4%)	0.35
Diabetes mellitus	63 (37.9%)	41 (35.7%)	22 (23.7%)	0.06
History of DVT	54 (25.1%)	14 (12.8%)	40 (37.7%)	0.001
History of surgery (>24 h)	48 (22.6%)	32 (29.4%)	16 (15.5%)	0.01
Hypercholesterolemia	44 (21.0%)	22 (19.0%)	22 (23.4%)	0.43
Coronary artery disease	32 (15.6%)	24 (21.4%)	8 (8.6%)	0.01
History of PE	31 (14.8%)	7 (6.7%)	24 (22.9%)	0.001
Bedridden	20 (9.4%)	17 (15.5%)	3 (2.9%)	0.002
Trauma	17 (8.0%)	14 (12.7%)	3 (2.9%)	0.008
Leg fracture	15 (7.1%)	13 (11.8%)	2 (1.9%)	0.005
Neck central line	15 (7.1%)	11 (10.1%)	4 (3.9%)	0.07
Ventilation perfusion scintigraphy	14 (6.6%)	6 (5.5%)	8 (7.7%)	0.52
Myocardial infarction	10 (4.9%)	9 (8.1%)	1 (1.1%)	0.02
Congestive heart failure	8 (3.9%)	5 (4.5%)	3 (3.3%)	0.65
Pelvic fracture	7 (3.3%)	6 (5.5%)	1 (1.0%)	0.06
Femoral central line	5 (2.4%)	4 (3.7%)	1 (1.0%)	0.19
History of surgery (<24 h)	4 (1.9%)	4 (3.7%)	0 (0.0%)	0.04
Paraplegia	1 (0.5%)	1 (0.9%)	0 (0.0%)	0.32

Note: *At least one marker positive for thrombophilia.

Table 2 Comparison of Clinical Probability Scores

Clinical Probability Scores	Overall (n=227)	Non-Thrombophilia (n=119)	Thrombophilia (n=108)	P value
Simplified Wells Score	0.92±0.74	0.90±0.73	0.94±0.75	0.64
High probability (>6)	0 (0.0%)	0 (0.0%)	0 (0.0%)	0.72 for all
Moderate probability (score 2–6)	44 (19.4%)	22 (18.5%)	22 (20.4%)
Low probability (<2)	183 (80.6%)	97 (81.5%)	86 (79.6%)
Revised Geneva Score	1.79±1.09	1.85±1.08	1.73±1.10	0.42
Low risk (score 0–3)	214 (94.3%)	112 (94.1%)	102 (94.4%)	0.91 for all
Intermediate risk (score 4–10)	13 (5.7%)	7 (5.9%)	6 (5.6%)
High risk (score ≥11)	0 (0.0%)	0 (0.0%)	0 (0.0%)
Simplified Pulmonary Embolism Severity Index (sPESI)	0 (0–2)	0 (0–2)	0 (0–2)	0.14
Low risk (0 point)	157 (69.2%)	78 (65.5%)	79 (73.1%)	0.21 for all
High risk (≥1 point)	70 (30.8%)	41 (34.5%)	29 (26.9%)

Figure 1 Distribution of thrombophilic disorders in patients with acute PE.

Figure 2 Occurrence of thrombophilia according to different age groups in patients with acute PE.

Table 3 Comparison of Management and Outcome

	Overall (n=227)	Non-Thrombophilia (n=119)	Thrombophilia* (n=108)	P value
D-Dimer (mg/L FEU), median, range (n=166)	4.5 (0.17–290)	6.6 (0.17–36.1)	3.9 (0.17–290)	0.04
Positive (>0.55 mg/L)	155 (93.4%)	74 (91.4%)	81 (95.3%)	0.30 for all
Negative	11 (6.6%)	7 (8.6%)	4 (4.7%)
Troponin T/I positivity (n=205)	132 (64.4%)	70 (64.8%)	62 (63.9%)	0.89
SVC/IVC thrombosis (n=200)	4 (2.0%)	NA	4 (4.8%)	–
Treatment**
Enoxaparin	164 (73.9%)	76 (65.0%)	88 (83.8%)	0.001
Warfarin	165 (74.7%)	72 (63.2%)	93 (86.9%)	0.001
Heparin	124 (55.4%)	69 (58.0%)	55 (52.4%)	0.40
Aspirin	91 (41.7%)	55 (47.4%)	36 (35.3%)	0.07
Dalteparin	39 (17.5%)	29 (24.4%)	10 (9.6%)	0.004
Warfarin for life	51 (22.6%)	16 (13.6%)	35 (32.4%)	0.001
Warfarin (<2 years)	86 (37.9%)	46 (38.7%)	40 (37.0%)	0.80
Warfarin (>2 years)	40 (17.6%)	12 (10.1%)	28 (25.9%)	0.002
Plavix	24 (10.8%)	17 (14.5%)	7 (6.6%)	0.05
Thrombolytic therapy	11 (4.9%)	4 (3.4%)	7 (6.5%)	0.28
Complications
Leg edema	44 (19.6%)	21 (17.9%)	23 (21.5%)	0.50
Pulmonary hypertension	37 (16.6%)	12 (10.3%)	25 (23.4%)	0.009
Calf pain	34 (15.2%)	15 (12.8%)	19 (17.9%)	0.29
Leg ulcer	6 (2.7%)	4 (3.4%)	2 (1.9%)	0.48
Hospital stay (days)	8 (1–240)	9.5 (1–240)	7.5 (1–65)	0.02
Duration of follow-up (days)	45.2 (1–5488)	32 (1–1245)	73.3 (1–5488)	0.03
Mortality	19 (8.4%)	14 (11.8%)	5 (4.6%)	0.05

Notes: *At least one marker positive for thrombophilia; **There is an overlap as one can receive two different medications.

Abbreviations: NA, not applicable; ALA, abnormal lupus anticoagulation.

Table 4 Presentation of Main Clinical Features of the Thrombophilic Defects

	PC Deficiency (n=76)	PS Deficiency (n=77)	AT III Deficiency (n=56)	Hyperhomocysteinemia (n=56)	ALA (n=32)	APS (n=11)	FVL (n=7)
Age (mean±SD)	44.1±13.8	44.5±13.7	45.5±13.8	45.4±12.9	43.2±12.8	38.2±11.7	51.4±14.3
Males	45 (59.2%)	45 (58.4%)	38 (67.9%)	40 (71.4%)	21 (65.6%)	7 (63.6%)	4 (57.1%)
Risk Factor/Comorbidity
Hypertension	18 (28.6%)	19 (29.7%)	17 (37.8%)	14 (30.4%)	9 (34.6%)	2 (22.2%)	4 (57.1%)
Diabetes mellitus	13 (20.6%)	13 (17.6%)	10 (22.2%)	12 (21.4%)	6 (23.1%)	2 (28.6%)	1 (14.3%)
History of DVT	27 (36.5%)	28 (36.8%)	22 (40.0%)	22 (39.3%)	13 (40.6%)	6 (54.5%)	2 (28.6%)
History of surgery (>24 h)	13 (18.1%)	13 (17.6%)	10 (22.2%)	7 (13.0%)	1 (3.1%)	1 (11.1%)	2 (28.6%)
Coronary artery disease	5 (7.9%)	4 (6.3%)	4 (8.9%)	3 (6.5%)	2 (6.5%)	0 (0.0%)	0 (0.0%)
History of PE	17 (23.0%)	19 (25.0%)	13 (23.6%)	12 (21.4%)	9 (29.0%)	3 (30.3%)	1 (14.3%)
Bedridden	1 (1.4%)	1 (1.4%)	1 (1.9%)	2 (3.7%)	2 (6.5%)	1 (11.1%)	0 (0.0%)
Trauma	3 (4.2%)	3 (4.1%)	2 (3.7%)	2 (3.7%)	1 (3.1%)	0 (0.0%)	0 (0.0%)
D-Dimer level (mg/L FEU), median, range	3.9 (0.17–290)	3.9 (0.74–290)	3.6 (0.17–290)	4.5 (0.17–290)	3.05 (0.30–290)	2.5 (0.17–16.9)	4.6 (0.85–12.3)
Positive D-dimer	63 (98.4%)	65 (84.4%)	44 (95.7%)	44 (97.8%)	26 (96.3%)	8 (80.0%)	6 (85.7%)
Troponin T/I positivity	44 (62.9%)	44 (62.9%)	32 (64.0%)	32 (64.0%)	17 (63.0%)	4 (57.1%)	4 (80.0%)
Mortality	2 (2.6%)	2 (2.6%)	2 (3.6%)	0 (0.0%)	1 (3.1%)	1 (9.1%)	0 (0.0%)

Abbreviations: PC, protein C; PS, protein S; AT III, antithrombin III; ALA, abnormal lupus anticoagulation; APS, antiphospholipid syndrome; FVL, factor V Leiden.

Table 5 Review of Literature for VTE and Thrombophilia

Author	Year	Population	Age	Sex M/F	AT III	PC	PS	FVL	Hyp-Hcy	Double/Multiple	VTE/PE	Outcome
Lee et al^Citation14	2017	222 (66)	50 (41–63)	109/7	14	12	4	NA	NA	NA	VTE	The prevalence of HT (unprovoked VTE) was 15%. Family history of VTE and young age (<45 years) were independent predictors for unprovoked VTE due to HT
Brüwer et al^Citation15	2016	144 688 Adult 321 Children 367	Age of the first VTE	Male children (58.8%); male adolescents (47.6%); male adults (55.9%)	23 child 23 adult	29 child 13 adult	33 child 23 adult	NA	NA	NA	VTE	Children and adults differ with respect to i) thrombotic locations, ii) percentage of unprovoked versus provoked VTE, and iii) different rates of positive VTE family histories
Bucciarelli et al^Citation16	1999	746	39.5 (1–95)	232/281	129	145 309 APCR	138	NA	NA	25	VTE	AT III deficiency seems to have a higher risk for VTE than the other genetic defects. There is a relationship between age and occurrence of thrombosis for both men and women
Lee et al^Citation17	2011	384	PC: 50.5 (23–76) PS: 44 (20–76) AT: 59.5 (23–83) FV: 30	151/233	14	4	31	1	NA	NA	VTE	In Singapore and countries with similar demographics, hereditary thrombophilia screening should be confined to testing for protein C, protein S and AT III
Brouwer et al^Citation18	2009	130 (90)	49 (21–89)	50/80	12	40	39	25 (19)	24 (20)	NA	VTE	Patients with a PS, PC, or AT III deficiency appear to have a high absolute risk of recurrence
Rossi et al^Citation19	2008	920 (198) DVT + PE 242 DVT 678	37 (1–85)	146 (16)	8 (3)	11 (3)	10 (3)	62 (19%)	NA	12 (4)	PE	Higher risk of symptomatic PE in patients with AT deficiency or PT G20210A. Risk decreased in those with FV Leiden in comparison with those with no known inherited defect
De Stefano et al^Citation20	2006	538 (64)	0–68	29/35	14	28	22	NA	NA	NA	VTE	Deficiency of AT, PC, or PS has a 1.5-fold increased risk of recurrent VTE; in particular, symptomatic patients with AT deficiency require indefinite anticoagulation
Martinelli et al^Citation21	1998	723 (396)	40±19	332/391	85 (12%)	64 (9%)	41 (6%)	200 (28%)	NA	6 (1%)	VTE	Factor V Leiden is associated with smaller risk of thrombosis (less severe thrombotic manifestations), than that for AT III, protein C, or protein S deficiency
Simioni et al^Citation22	1999	405 (793)	41 (2–80) 42 (6–95) for factor V	80/101 105–119	34	73	74	224	NA	NA	VTE	Screening family members of symptomatic carriers of AT III, PC, and PS deficiency is needed. For family members of symptomatic carriers of factor V Leiden, screening does not seem to be justified except for women of fertile age
Current study	–	227	50.6±16.9	125/102	56	76	77	7	56	–	PE	A total of 108 (47.6%) patients were found to have thrombophilia. Deficiency of protein S, protein C, and antithrombin III are the leading causes of thrombophilic defects. Patients with hereditary thrombophilia are at increased risk of acute PE, particularly,among young individuals (<40 years)

Abbreviations: NA, not available; HT, hereditary thrombophilia.

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