Thromboprophylaxis after intracerebral hemorrhage [Neurosurgery Wiki]

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====== Thromboprophylaxis after intracerebral hemorrhage ======

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1j_AM05Yvo4jA0yVz_FvBwT0IvqgJy4f0LW16_XI1cgod6bQ4S/?limit=15&utm_campaign=pubmed-2&fc=20230907042444}}

===== Intermittent pneumatic compression after intracerebral hemorrhage =====


see [[Intermittent pneumatic compression after intracerebral hemorrhage]]

[[Intermittent pneumatic compression]] device beginning the day of admission to prevent [[DVT]] (Level I
((Hemphill JC,3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015; 46:2032–2060))
). 

✖ not recommended: graduated compression device to prevent DVT or improve outcome (Level III
((Hemphill JC,3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015; 46:2032–2060))
).

2. after documentation of cessation of bleeding: consider low dose sub-Q heparin ([[LMW]] or [[unfractionated]]) to prevent DVT in patients with lack of mobility after 1–4 days from ICH (Level II
((Hemphill JC,3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015; 46:2032–2060))
).

3. for patients with symptomatic DVT or [[PE]]: systemic [[anticoagulation]] or [[inferior vena cava filter]] placement is probably indicated (Level II
((Hemphill JC,3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015; 46:2032–2060))
). 
The choice of modality should consider the time from [[ICH]], ICH stability, cause of ICH & overall patient condition (Level II
((Hemphill JC,3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015; 46:2032–2060))
).
----
Oral anticoagulant (OAC) resumption does not increase the risk of recurrent ICH and can also reduce the risk of all-cause mortality. OAC cessation exposes patients to a significantly higher risk of [[thromboembolism]], which could be reduced by resumption. The optimal timing of [[anticoagulation resumption]] after ICH is still unknown. Both early (< 2 weeks) and late (> 4 weeks) resumption should be reached only after very careful assessment of risks for ICH recurrence and thromboembolism. The introduction of new oral anticoagulants and other interventions, such as left atrial appendage closure, has provided some patients with more alternatives. Given the lack of high-quality evidence to guide clinical decision-making, clinicians must carefully balance the risks of thromboembolism and recurrent ICH in individual patients. 

Li and Lip proposed a management approach which would facilitate the decision-making process on whether anticoagulation is appropriate, as well as when and how to restart anticoagulation after ICH
((Li YG, Lip GYH. Anticoagulation Resumption After Intracerebral Hemorrhage.
Curr Atheroscler Rep. 2018 May 21;20(7):32. doi: 10.1007/s11883-018-0733-y.
Review. PubMed PMID: 29781063; PubMed Central PMCID: PMC5960649.
)).
----


Given the high risk of [[hematoma expansion]] in the early phase of acute [[ICH]], most experts recommend reversing [[anticoagulation]] immediately.

Many clinicians start subcutaneous [[heparin]]oids in low doses 24 to 72 hours after ICH to prevent [[deep vein thrombosis]], and after the first few days or a week, consider either increasing the dose to a full [[anticoagulation]] dose or making a transition to oral [[anticoagulant]]s.

Many patients with lobar [[hemorrhage]] or [[cerebral amyloid angiopathy]] may remain at higher risk of anticoagulant-related ICH recurrence than [[thromboembolic event]]s and would therefore be best managed without anticoagulants.

Those with deep hemispheric ICH, [[hypertension]] that can be well controlled, and a high risk of disabling thromboembolism may receive net benefit from restarting anticoagulation.

Urgent reversal of anticoagulation is standard in the acute phase of ICH

The proposed ‘spot-sign score’ may predict both expansion and poor outcome. see [[Computed Tomography Angiography spot sign]]

Antihypertensive therapy likely reduces the risk of recurrence in patients with hypertensive hemorrhage

Most patients with anticoagulation-related ICH have a presenting INR within the therapeutic range

The risks of restarting warfarin are high on the first day, but much lower after several days
((Goldstein JN, Greenberg SM. Should anticoagulation be resumed after
intracerebral hemorrhage? Cleve Clin J Med. 2010 Nov;77(11):791-9. doi:
10.3949/ccjm.77a.10018. Review. PubMed PMID: 21048052; PubMed Central PMCID:
PMC3684182.
)).
----
A mainstay of medical [[management]] in [[ICH]] is [[prevention]] of [[venous thromboembolism]] (VTE), including [[deep venous thrombosis]] (DVT) and [[pulmonary embolism]] (PE). Patients with ICH are at high risk for DVT and PE, with 4-fold higher rates than in patients with [[acute ischemic stroke]]

[[Venous thromboembolism]] (VTE) is common after [[intracerebral hemorrhage]] (ICH). [[Guideline]]s recommend early VTE [[prophylaxis]]
((Gregory PC, Kuhlemeier KV. Prevalence of venous thromboembolism in
acute hemorrhagic and thromboembolic stroke. Am J Phys Med Rehabil.
2003;82:364–369. doi: 10.1097/01.PHM.0000064725.62897.A5.))
((Masotti L, Godoy DA, Napoli MD, Rabinstein AA, Paciaroni M, Ageno
W. Pharmacological prophylaxis of venous thromboembolism during
acute phase of spontaneous intracerebral hemorrhage: what do we know
about risks and benefits? Clin Appl Thromb Hemost. 2012;18:393–402.
doi: 10.1177/1076029612441055.)).

[[American Heart Association]]/ [[American Stroke Association]] [[guideline]]s have recommended low-dose unfractionated [[heparin]] or low-molecular weight heparin use early after ICH since [[2007]]
((Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D,
et al; American Heart Association/American Stroke Association Stroke
Council; American Heart Association/American Stroke Association
High Blood Pressure Research Council; Quality of Care and Outcomes in
Research Interdisciplinary Working Group. Guidelines for the management
of spontaneous intracerebral hemorrhage in adults: 2007 update:
a guideline from the American Heart Association/American Stroke
Association Stroke Council, High Blood Pressure Research Council,
and the Quality of Care and Outcomes in Research Interdisciplinary
Working Group. Circulation. 2007;116:e391–e413. doi: 10.1161/
CIRCULATIONAHA.107.183689.)).
and currently recommend initiation between 1 and 4 days after ICH onset and after cessation of active bleeding (class IIb, level of evidence B)
((Morgenstern LB, Hemphill JC III, Anderson C, Becker K, Broderick
JP, Connolly ES Jr, et al; American Heart Association Stroke Council
and Council on Cardiovascular Nursing. Guidelines for the management
of spontaneous intracerebral hemorrhage: a guideline for healthcare
professionals from the American Heart Association/American
Stroke Association. Stroke. 2010;41:2108–2129. doi: 10.1161/
STR.0b013e3181ec611b.)).

Multiple studies have observed that [[hematoma expansion]] is infrequently encountered after the first 24 to 48 hours in spontaneous patients with [[ICH]]
((Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L, et
al. Early hemorrhage growth in patients with intracerebral hemorrhage.
Stroke. 1997;28:1–5.))
((Jauch EC, Lindsell CJ, Adeoye O, Khoury J, Barsan W, Broderick J, et
al. Lack of evidence for an association between hemodynamic variables
and hematoma growth in spontaneous intracerebral hemorrhage. Stroke.
2006;37:2061–2065. doi: 10.1161/01.STR.0000229878.93759.a2.)).

In contrast, clinically evident [[VTE]] occurs in up to 13% of patients with [[ICH]], peaks
between days 2 and 7 of hospitalization, and carries a high risk of fatality because of [[PE]]
((Skaf E, Stein PD, Beemath A, Sanchez J, Bustamante MA, Olson
RE. Venous thromboembolism in patients with ischemic and hemorrhagic
stroke. Am J Cardiol. 2005;96:1731–1733. doi: 10.1016/j.
amjcard.2005.07.097.))
((André C, de Freitas GR, Fukujima MM. Prevention of deep
venous thrombosis and pulmonary embolism following stroke: a systematic review of published articles. Eur J Neurol. 2007;14:21–32.
doi: 10.1111/j.1468-1331.2006.01536.x.))
((Brandstater ME, Roth EJ, Siebens HC. Venous thromboembolism in
stroke: literature review and implications for clinical practice. Arch Phys
Med Rehabil. 1992;73(5-S):S379–S391.))
((Ogata T, Yasaka M, Wakugawa Y, Inoue T, Ibayashi S, Okada Y. Deep
venous thrombosis after acute intracerebral hemorrhage. J Neurol Sci.
2008;272:83–86. doi: 10.1016/j.jns.2008.04.032.)).
However, large randomized clinical trials of pharmacological DVT prophylaxis in patients with ICH have not been conducted. Several observational and nonrandomized studies have indicated that low-dose anticoagulation does not result in hematoma expansion after ICH
((Wu TC, Kasam M, Harun N, Hallevi H, Bektas H, Acosta I, et al.
Pharmacological deep vein thrombosis prophylaxis does not lead
to hematoma expansion in intracerebral hemorrhage with intraventricular
extension. Stroke. 2011;42:705–709. doi: 10.1161/
STROKEAHA.110.600593.))
((Wasay M, Khan S, Zaki KS, Khealani BA, Kamal A, Azam I, et al.
A non-randomized study of safety and efficacy of heparin for DVT
prophylaxis in intracerebral haemorrhage. J Pak Med Assoc. 2008;58:
362–364.))
((Harvey RL, Lovell LL, Belanger N, Roth EJ. The effectiveness of anticoagulant
and antiplatelet agents in preventing venous thromboembolism
during stroke rehabilitation: a historical cohort study. Arch Phys Med
Rehabil. 2004;85:1070–1075.))
((Kleindienst A, Harvey HB, Mater E, Bronst J, Flack J, Herenz K, et al.
Early antithrombotic prophylaxis with low molecular weight heparin in
neurosurgery. Acta Neurochir (Wien). 2003;145:1085–1090, discussion
1090. doi: 10.1007/s00701-003-0142-y.))
((Kiphuth IC, Staykov D, Köhrmann M, Struffert T, Richter G, Bardutzky
J, et al. Early administration of low molecular weight heparin after spontaneous
intracerebral hemorrhage. A safety analysis. Cerebrovasc Dis.
2009;27:146–150. doi: 10.1159/000177923.))
((Tetri S, Hakala J, Juvela S, Saloheimo P, Pyhtinen J, Rusanen H, et
al. Safety of low-dose subcutaneous enoxaparin for the prevention of
venous thromboembolism after primary intracerebral haemorrhage.
Thromb Res. 2008;123:206–212. doi: 10.1016/j.thromres.2008.01.018.)).
----
In an analysis of the Premier database, Prabhakaran et al. identified adult patients with ICH (International Classification of Diseases Ninth edition code 431) from 2006 to 2010 who survived to day 2 of hospitalization. They excluded those with trauma or who underwent craniotomy or angiography. They abstracted type of anticoagulant used and date of first administration. They used univariate statistics and multivariable logistic regression to assess factors associated with prophylactic anticoagulation after ICH.

Among 32 690 (mean age, 69.7 years; 50.1% men) patients with spontaneous ICH, 5395 (16.5%) patients received any prophylactic anticoagulation during the hospital stay. Among these patients, 2416 (44.8%) received prophylactic anticoagulation by day 2. The most commonly used agents were heparin (71.1%), enoxaparin (27.5%), and dalteparin (1.4%). The proportion of patients receiving prophylactic anticoagulation increased slightly during the study period from 14.3% to 18.0% (P<0.01 for trend). Use of prophylactic anticoagulation varied by geographic region (P<0.001) in the United States: Northeast (23.2%), South (19.0%), Midwest (10.8%), and West (9.8%). In multivariable analysis, geographic region remained an independent predictor of prophylactic anticoagulation.

Less than 20% of patients with ICH receive anticoagulation for deep venous thrombosis in the United States. When used, the time to initiation is <2 days in less than half of the patients. Further study should focus on understanding variations in practice and emphasize guideline-driven care
((Prabhakaran S, Herbers P, Khoury J, Adeoye O, Khatri P, Ferioli S, Kleindorfer
DO. Is prophylactic anticoagulation for deep venous thrombosis common practice
after intracerebral hemorrhage? Stroke. 2015 Feb;46(2):369-75. doi:
10.1161/STROKEAHA.114.008006. Epub 2015 Jan 8. PubMed PMID: 25572413.
)).
===== Case series =====

Ianosi et al. from the Institute of Medical Informatics, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall, Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Department of Clinical and Experimental Medicine, University of Sassari, Italy,
Department of Neuroradiology, Medical University of Innsbruck, Department of Neurosurgery, Medical University of [[Innsbruck]], [[Austria]], analyzed 134 consecutive [[patient]]s admitted to a [[tertiary]] [[neurointensive care]] unit with diagnosed [[spontaneous intracerebral hemorrhage]], obtained [[informed consent]] and without previous [[anticoagulation]], a severe [[coagulopathy]], hematoma evacuation, early withdrawal of therapy or ineligibility for [[DVT]] [[prophylaxis]] according to there institutional [[protocol]]. Significant late [[hematoma expansion]] (HE) was defined as ≥6mL increase of [[hematoma]] [[volume]] between [[neuroimaging]] within 48h and day 3-6. [[Multivariate analysis]] was performed to identify risk factors for late HE, poor 3-month [[outcome]] (mRS≥4) and [[mortality]].

Patients had a median [[Glasgow Coma Scale]] [[Score]] of 14 (IQR 10-15), [[ICH]] volume of 11mL (IQR 5-24) and were 71 years old (IQR 61-76). 56% (N=76) received early DVT prophylaxis, 37% (N=50) late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume (9.5mL, IQR 4-18.5; versus 17.5mL, IQR 8-29; p=0.038) and more often were comatose (26% versus 10%, p=0.025). Significant late HE (N=5/134, 3.7%) was associated with larger initial ICH volume (p=0.02) and lower thrombocyte count (p=0.03) but not with early DVT prophylaxis (p=0.36). Early DVT prophylaxis was not associated with worse outcome.

Significant late HE is uncommon and DVT prophylaxis within 48h of symptom onset may be safe in selected ICH patients
((Ianosi B, Gaasch M, Rass V, Huber L, Hackl W, Kofler M, Schiefecker AJ, Addis 
A, Beer R, Rhomberg P, Pfausler B, Thomé C, Ammenwerth E, Helbok R. Early
thrombosis prophylaxis with enoxaparin is not associated with hematoma expansion 
in patients with spontaneous intracerebral hemorrhage. Eur J Neurol. 2018 Oct 11.
doi: 10.1111/ene.13830. [Epub ahead of print] PubMed PMID: 30308696.
)).
----
To determine characteristics associated with early chemoprophylaxis (CP) after ICH in the Get With The Guidelines-Stroke registry.
METHODS:

In this observational cohort study, we identified patients with ICH between January 1, 2009 and September 30, 2013, who (1) were non-ambulatory and/or not comfort care measures by hospital day 2; (2) were not transferred to another acute care facility; and (3) had known VTE prophylaxis status at end of hospital day 2. Categories for VTE prophylaxis were as follows: (1) mechanical non-CP or (2) CP with or without mechanical prophylaxis. Early prophylaxis was defined as occurring by hospital day 2. Using multivariable logistic regression, we assessed patient, hospital, and geographic factors independently associated with early CP use.
RESULTS:

Among 74 283 patients with ICH from 1358 hospitals, 5929 (7.9%) received early CP, 66 444 (89.4%) received early mechanical/non-CP, and 1910 (2.6%) had no prophylaxis, mechanical or CP, within the first 2 days. There was no increase in early CP use over the study period; 60% of hospitals provided early CP to <9% of patients. In multivariable analysis, female sex, atrial fibrillation, diabetes, coronary, carotid, and peripheral artery disease, prior ischemic stroke or transient ischemic attack, hospital size >500 beds, and geographic region were independently associated with early vs no early CP use.
CONCLUSION:

Nationwide, the large majority of ICH patients receive early mechanical VTE prophylaxis only, without CP. Patient comorbidities and hospital characteristics such as geographic location are determinants of higher use of early CP
((Cherian LJ, Smith EE, Schwamm LH, Fonarow GC, Schulte PJ, Xian Y, Wu J,
Prabhakaran SK. Current Practice Trends for Use of Early Venous Thromboembolism
Prophylaxis After Intracerebral Hemorrhage. Neurosurgery. 2018 Jan 1;82(1):85-92.
doi: 10.1093/neuros/nyx146. PubMed PMID: 28379461.
)).
----
Wu et al. identified patients from ther stroke registry (6/03 to 12/07) who presented with ICH only or ICH + intraventricular hemorrhage (IVH) and received either LMWH SQ or UH within 7 days of admission and had a repeat CT scan performed within 4 days of starting DVT prophylaxis. We calculated the change in hematoma volume (Δvol) from the admission and post treatment CTs. HV was calculated using the (ABC/2) method and IVH volumes were calculated using a published method of hand drawn regions of interest (ROI)

They identified 73 patients with a mean age of 63 yo and median NIHSS 11.5. The mean baseline total HV was 25.8ml ± 23.2ml. There was an absolute Δvol from pre and posttreatment CT of −4.3ml ± 11.0ml. Two patients developed hematoma growth. Repeat analysis of patients given pharmacological DVT prophylaxis within 2 or 4 days after ICH found no increase in hematoma size.

Pharmacological DVT prophylaxis given SQ in patients with ICH and/or IVH in the subacute period is generally not associated with hematoma growth
((Wu T-C, Kasam M, Harun N, et al. Pharmacological DVT Prophylaxis Does Not Lead to Hematoma Expansion in Intracerebral Hemorrhage with Intraventricular Extension. Stroke; a journal of cerebral circulation. 2011;42(3):10.1161/STROKEAHA.110.600593. doi:10.1161/STROKEAHA.110.600593.)).

===== References =====