venous_thromboembolism_in_high-grade_glioma

Venous thromboembolism in high-grade glioma

Therapeutic anticoagulation is associated with a 7-fold increase risk of ICH in glioma patients. Data emerging from a study support the need for high-quality studies to evaluate the risk of ICH in patients with glioma and VTE 1).

Venous thromboembolism (VTE) is a common complication in patients with high-grade gliomas, occurring in approximately 24-30% of such patients 2) 3) 4) 5).


In a study of Senders et al. from Boston and Utrecht, patients were extracted from the National Surgical Quality Improvement Program registry (2005-2015) and analyzed using multivariable logistic regression.

A total of 7376 patients were identified, of which 948 (12.9%) experienced a major complication. The most common major complications were reoperation (5.1%), venous thromboembolism (3.5%), and death (2.6%). Furthermore, 15.6% stayed longer than 10 d, and 11.5% were readmitted within 30 d after surgery. The most common reasons for reoperation and readmission were intracranial hemorrhage (18.5%) and wound-related complications (11.9%), respectively. Multivariable analysis identified older age, higher body mass index, higher American Society of Anesthesiologists (ASA) classification, dependent functional status, elevated preoperative white blood cell count (white blood cell count WBC, >12 000 cells/mm3), and longer operative time as predictors of major complication (all P < .001). Higher ASA classification, dependent functional status, elevated WBC, and ventilator dependence were predictors of extended length of stay (all P < .001). Higher ASA classification and elevated WBC were predictors of reoperation (both P < .001). Higher ASA classification and dependent functional status were predictors of readmission (both P < .001). Older age, higher ASA classification, and dependent functional status were predictors of death (all P < .001).

This study provides a descriptive analysis and identifies predictors for short-term complications, including death, after craniotomy for primary malignant brain tumors 6).

To determine the rate of ICH in patients treated with enoxaparin, we performed a matched, retrospective cohort study with blinded radiology review for 133 patients with high-grade glioma. After diagnosis of glioma, the cohort that received enoxaparin was 3 times more likely to develop a major ICH than those not treated with anticoagulation (14.7% vs 2.5%; P = .036; hazard ratio [HR], 3.37; 95% confidence interval [CI], 1.02-11.14). When enoxaparin was analyzed as a time-varying covariate, anticoagulation was associated with a >13-fold increased risk of hemorrhage (HR, 13.26; 95% CI, 3.33-52.85; P < .0001). Overall survival was significantly shorter for patients who suffered a major ICH on enoxaparin compared with patients not receiving anticoagulation (3.3 vs 10.2 months; log-rank P = .012). We applied a validated ICH prediction risk score PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke), and observed that all major ICHs on enoxaparin occurred in the setting of a PANWARDS score ≥25, corresponding with a sensitivity of 100% (95% CI, 63% to 100%) and a specificity of 40% (95% CI, 25% to 56%). We conclude that caution is warranted when considering therapeutic anticoagulation in patients with high-grade gliomas given the increased risk of ICH and poor prognosis after a major hemorrhage on anticoagulation. The PANWARDS score may assist clinicians in identifying the patients at greatest risk of suffering a major intracranial hemorrhage with anticoagulation 7).


Platelets, ×109/L <125

11  

125–149

8  

150–174

5  

175–199

3  

≥200

0

Albumin, g/dL  

<3.0

18

3.0–3.49

14  

3.5–3.99

9  

4.0–4.49

5  

≥4.5

0

No history of CHF

6

Warfarin instead of rivaroxaban

7

Age, y  

<55

0

  55–64

4

  65–74

8

  75–84

13

  ≥85

17

Race

  Black

18

  Asian

9

  White or other

0

Diastolic blood pressure, mm Hg

  <50

0

  50–69

4  

70–89

9

  90–109

13

  ≥110

17

Previous stroke or TIA

5

CHF indicates congestive heart failure; PANWARDS, platelets, albumin, no CHF, warfarin, age, race, diastolic blood pressure, stroke; and TIA, transient ischemic attack.


1)
Al Megren M, De Wit C, Al Qahtani M, Le Gal G, Carrier M. Management of venous thromboembolism in patients with glioma. Thromb Res. 2017 Aug;156:105-108. doi: 10.1016/j.thromres.2017.06.010. Epub 2017 Jun 8. PubMed PMID: 28624717.
2)
Brandes AA, Scelzi E, Salmistraro G, et al.: Incidence of risk of thromboembolism during treatment high-grade gliomas: a prospective study. Eur J Cancer 33: 1592-1596, 1997.
3)
Dhami MS, Bona RD, Calogero JA, et al.: Venous thromboembolism and high-grade gliomas. Thromb Haemost 70: 393-396, 1993.
4)
Marras LC, Geerts WH, Perry JR: The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Cancer 89: 640-646, 2000.
5)
Quevedo JF, Buckner JC, Schmidt JL, et al.: Thromboembolism in patients with high-grade glioma. Mayo Clin Proc 69: 329-332, 1994
6)
Senders JT, Muskens IS, Cote DJ, Goldhaber NH, Dawood HY, Gormley WB, Broekman MLD, Smith TR. Thirty-Day Outcomes After Craniotomy for Primary Malignant Brain Tumors: A National Surgical Quality Improvement Program Analysis. Neurosurgery. 2018 Dec 1;83(6):1249-1259. doi: 10.1093/neuros/nyy001. PubMed PMID: 29481613.
7)
Mantia C, Uhlmann EJ, Puligandla M, Weber GM, Neuberg D, Zwicker JI. Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin. Blood. 2017 Jun 22;129(25):3379-3385. doi: 10.1182/blood-2017-02-767285. Epub 2017 May 3. PubMed PMID: 28468796.
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