“Initial Treatment Of Malignant Glioma In Older Adults”. Uptodate.com. 2017. Accessed 8 Mar. 2017.
Kovacs, Michael J. “Comparison Of 10-Mg And 5-Mg Warfarin Initiation Nomograms Together With Low-Molecular-Weight Heparin For Outpatient Treatment Of Acute Venous Thromboembolism”.Annals of Internal Medicine 138.9 (2003): 714.
- Anticoagulate in patients with brain tumors and VTE except if risk of ICH is high: i.e.
- melanoma mets
- renal cell carcinoma mets
- choriocarcinoma mets
- thyroid carcinoma mets
- treat x 3-6 months; long term if malignant gliomas
- LMWH recommended versus warfarin
- If risk of ICH high:
- IVC filter if significant residual brain mets
- if mets already removed / treated effectively and medical condition too unstable – anticoagulate
- do not anticoagulate except in post-operative period
- use SCDs with post-op LMWH or UFH 12-24 hours after surgery
- cotninue prophylaxis until ambulation resumed
Uptodate. “Anticoagulant and antiplatelet therapy in patients with brain tumors.” Accessed 08/12/2016.
Lyman GH, Khorana AA, Falanga A, et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007; 25:5490.
VerifyNow for Clopidogrel:
- Values less than 194 PRU are specific evidence of a P2Y12 inhibitor effect
VerifyNow for Aspirin:
- ≤ 549: Evidence of platelet dysfunction due to aspirin
- > 550: No evidence of aspirin-induced platelet dysfunction
ASA-specific VerifyNow uses arachidonic acid as an agonist for platelet aggregation onto fibrinogen-coated beads.
VerifyNow (P2Y12) uses adenosine diphosphate and is more commonly utilized to detect platelet dysfunction due to clopidogrel.
Degree of platelet aggregation is recorded as aspirin reaction units (ARUs) or P2Y12 reaction units (PRUs).
Abnormally functiong platelets are defined as ARU <550 or PRU 208 (U of Cincinnati lab normal value, cutoff not universally defined).
VerifyNow Reference Guide
Clinical Value of the VerifyNow System
Martin, G., Shah, D., Elson, N., Boudreau, R., Hanseman, D., Pritts, T., Makley, A., Foreman, B. and Goodman, M. (2018). Relationship of Coagulopathy and Platelet Dysfunction to Transfusion Needs After Traumatic Brain Injury. Neurocritical Care.
Checklist for hypercoagulable work-up
- *Antithrombin III Activity
- *Prothrombin Gene Mutation
- *Factor V (5) Leiden Gene Mutation
- Factor VIII (8) Activity
- aPTT-LA (Lupus Sensitive Reagent)
- Anticardiolipin Antibody (IgG, IgM, IgA)
- Beta 2 glycoprotein
- Russell Viper Venom Time (dilute)
- *Protein C Activity
- *Protein S Activity
- ESR CRP ANA
- Lipoprotein A
- Plasminogen activator inhibitor
*Shani list, also add Lupus anticoagulant, Vit B12 levels
- Alpha-macroglobulin deficiency
- Factor V deficiency, excess
- Factor VII excess
- Factor VIII excess
- Factor XI excess
- Heparin cofactor II deficiency
- PAI-1 excess
- Plasminogen deficiency
- tPA deficiency
- TFPI deficiency
- Thrombomodulin deficiency
“Hypercoagulability Panel – Machaon Diagnostics”. Machaon Diagnostics. N.p., 2016. Web. 30 Mar. 2016.
“Hypercoagulable States”. Clevelandclinicmeded.com. N.p., 2016. Web. 30 Mar. 2016.
Pathogenesis: production of VEGF, glutamate, leukotrienes (increases permeability of tumor vessels) and absence of tight endothelial cell junctions in tumor blood vessels (respond to VEGF and basic fibroblast growth factor)
Gliomas, meningiomas, metastatic tumors –> secretes VEGF –> binds to VEGFR1 and VEGFR2 (surface of endothelial cells –> formation of gaps in endothelium –> fluid leakage into brain parenchyma –> vasogenic edema –> spreads more in white matter (lower resistance than gray matter) –> disrupts synaptic transmission, alters neuronal excitability –> HA, seizures, focal deficits, encephalopathy, herniation
Advantages: Lack of mineralocorticoid activity, less fluid retention; lower risk of infection and cognitive impairment
Mechanism: Upregulates Ang-1 (BBB-stabilizing factor) and downregulates VEGF in astrocytes and pericytes; increases clearance of peritumoral edema by facilitating transport of fluid into ventricular system
- Severe symptoms: 10mg IV loading dose then 4mg QID or 8 mg BID
- Lower doses (1-2mg QID) may be as effective and less toxic
- Long half life allows BID dosing
- Improves within hours, maximum benefit within 24-72 hours, neuroimaging may not confirm until at least 1 week
- If 16mg/day insufficient, may increase up to 100mg/day
- Taper: once improved, taper by 50% every 4 days
- severe symptoms: 16mg/d or more
- milder symptoms: start 4-8mg daily
- asymptomatic: steroids not recommended
- taper over 2 week period or longer
- Insomnia, essential tremor, hiccups
- GI complications
- Steroid myopathy – prox weakness in week 9-12
- PCP infection – risk increases while tapering steroids; fever and dyspnea and dry cough but can be subtle and nonspecific
- bevacizumab (anti-VEGF monoclonal antibodies)
- corticotrophin-releasing factor
- COX-2 inhibitors?
beta lactam Abx, sulfonamides, bactrim, vancomycin, linezolid, piperacillin, levofloxacin?VPA, phenytoin, CMZ, haldol?
ibuprofen?, naproxen?, acetaminophen?