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Therapeutic Subcutaneous Heparin for Treatment of Venous Thromboembolism

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Jose Nery

on 17 February 2014

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Transcript of Therapeutic Subcutaneous Heparin for Treatment of Venous Thromboembolism

2004
2006
TODAY
2012
1992
SC UFH versus IV UFH
Meta-analysis comparing efficacy and safety of SC UFH versus IV UFH

SC UFH more effective than continuous IV UFH for prevention of extension and recurrence of VTE
RR = 0.62; 95% CI (0.39 to 0.98)

SCH UFH as safe as continuous IV UFH in the occurrence of major hemorrhage
RR = 0.79; 95% CI (0.42 to 1.48)
SC Dose-Adjusted UFH versus Fixed-Dose LMWH
Patient population: 720 patients, average age 65.7 in the UFH group and 67.0 in the LMWH group, with acute symptomatic VTE
Fixed-Dose Weight-Adjusted SC UFH versus LMWH Heparin
Patient Population: 708 patients, average age 60 years old with acute venous thromboembolism
CHEST Guideline Recommendations
Antithrombotic Therapy for VTE Disease
Initial anticoagulation for patients with acute DVT of the leg, we recommend initial treatment with parenteral anticoagulation (LMWH, fondaparinux, IV UFH, or SC UFH)

Evidence-Based Management of Anticoagulation Therapy
For outpatients with VTE treated with subcutaneous (SC) UFH, we suggest weight-adjusted dosing (first dose 333 units/kg, then 250 units/kg) without monitoring rather than fixed or weight-adjusted dosing with monitoring.
SC UFH for the Treatment of DVT
Kearon C. CHEST Journal. 2012;141(2_suppl):e419S-e494S.
Holbrook A. CHEST Journal. 2012;141(2_suppl):e152S-e184S.

Hommes DW. Annals of internal medicine. Feb 15 1992;116(4):279-284.
Prandoni P. Archives of internal medicine. May 24 2004;164(10):1077-1083.

Kearon C. JAMA. Aug 23 2006;296(8):935-942.

Product Availability
10,000 units/mL
20,000 units/mL

Maximum volume of 1 mL for a subcutaneous injection
Patient Counseling
Dosing regimen
Appropriate drawing up of doses
Proper injection technique
Importance of rotating injection sites
Importance of medication adherence
Signs and symptoms of bleeding
SC UFH versus IV UFH
Figure 1. Efficacy (prevention of the extension and recurrence of venous thromboembolism) of initial heparin treatment by intravenous compared with subcutaneous administration for deep venous thrombosis.
Hommes DW. Annals of internal medicine. Feb 15 1992;116(4):279-284.
Figure 2. Safety (occurrence of major hemorrhage) of initial heparin treatment by intravenous compared with subcutaneous administration for deep venous thrombosis.
Treatment
Protocol
Prandoni P. Archives of internal medicine. May 24 2004;164(10):1077-1083.

SC UFH with dose adjusted by aPTT time by means of a weight-based algorithm is as effective and safe as fixed-dose nadroparin for initial treatment of VTE
Fixed-dose SC unfractionated heparin is as effective and safe as LMWH heparin in patients with acute VTE and is suitable for outpatient treatment
Timeline of Evidence-Based Literature Supporting the Use of Subcutaneous (SC) Unfractionated Heparin
Outpatient Treatment
Criteria in which outpatient treatment may not be appropriate:
Presence of massive DVT (iliofemoral)
Presence of symptomatic pulmonary embolism
High risk bleeding with anticoagulation therapy
Presence of comorbid conditions or other factors that may warrant inpatient stay
46 yo F w/ probable IJ and LE DVT
PMH: Breast cancer, HTN, depression, DM, MI s/p stent, hypothyroidism
Complex and complicated hospital course
AKI on HD
Ileostomy and colostomy
Previous thromboses in IVC and bilateral lower extremity
Inpatient Medications

Scheduled Medications
albuterol-ipratropium (DuoNeb 3 mg-0.5 mg/3 ml inhalation soln) 3mL Aerosol QID
aspirin 81mg Fdngtube Daily
atorvastatin (Lipitor) 40mg GastricTub QPM
buPROPion (Wellbutrin) 112.5mg NG Tube BID
ergocalciferol (Vitamin D (ergocalciferol)-nonformulary) 50,000Unit(s) Fdngtube Weekly
folic acid 1mg Fdngtube Daily
gabapentin (Neurontin) 200mg Fdngtube Daily
haloperidol (Haldol) 1mg IVP BID
insulin regular (HumuLIN R, NovoLIN R) (Insulin Sliding Scale) 0-12 Units subQ Q6H
lansoprazole 30mg NG Tube Daily
levothyroxine 125 mcg + SYRINGE (Synthroid 125 mcg + SYRINGE 1 ea) 125mcg IVP QAM
LIDOCAINE REMOVE PATCH Patch (Remove topical medication) 1ea Misc Q24H
lidocaine topical Patch 5% (Lidoderm 5% topical patch) 1Patch Topically Daily
methadone 16mg GastricTub Q8H
metoprolol (metoprolol immediate release) 12.5mg By Mouth QMndWedFri
metoprolol (metoprolol immediate release) 12.5mg By Mouth BIDTueThu
metoprolol (metoprolol immediate release) 12.5mg By Mouth BIDSatSun
nystatin topical (nystatin 100,000 units/g topical powder) 1Application Topically BID
polyethylene glycol 3350 (MiraLax) 17gm By Mouth Daily
senna (Senokot) 10mL Duotube AtBedtime
Inpatient Medications

PRN Medications
albuterol-ipratropium (DuoNeb 3 mg-0.5 mg/3 ml inhalation soln) 3mL Aerosol Q2H
alteplase 2 mg + SYRINGE (Alteplase (Cathflo) 2 mg + SYRINGE 1 ea) 2mg ClottCath As DirCPOE
glucose 50% (Dextrose 50% Injection 50 mL) 25gm IV As DirCPOE
haloperidol (Haldol) 2.5mg IVP Q6H
HYDROmorphone (Dilaudid) 2mg IVP Q1H
LORazepam (Ativan) 1mg IVP AtBedtime
midodrine (ProAmatine) 10mg By Mouth Daily
ondansetron (Zofran) 4mg IVP Q6H
phenol topical (Chloraseptic Spray) 5Spray(s) By Mouth Q2H

Continuous Infusions
AMINO ACID/DEXTROSE TPN (ADULT) 1,313.28 mL Initial Rate= 54.72mL/hr IV
AMINO ACID/DEXTROSE/LIPID TPN (ADULT) 1,547.53 mL + multivitamin 10 mL Initial Rate= 64.48mL/
hr IV
heparin 25,000 Unit(s) [18 unit(s)/kg/hr] + Base solution 250 mL Initial Rate= 15.3mL/hr IV


Patient Weight: 80 kg

Complicated bowel anatomy
Renal failure on HD

What is the best treatment for this patient's thrombosis?
LMWH Group: Nadroparin SC
85 U/kg twice daily
Treatment Protocol
UFH Group:
333 U/kg followed by subsequent doses of 250 U/kg twice daily

LMWH Group:
100 IU/kg dalteparin or enoxaparin
Additional Findings
Lack of an association between:
Low aPTT results and recurrent venous thromoboembolism
High aPTT results and bleeding

aPTT monitoring is not required with this dosing regimen

>75% of patients in each group partially or completely treated as outpatients
Adapted from: Franco-Martinez V et al. Subcutaneous Unfractionated Heparin for VTE Treatment In Patients on Dialysis or Who Are Not Candidates for Low Molecular Weight Heparins and Fondaparinux. University Health System. August 2012.
Monitored Dosing Approach

1. Calculate 24 hour IV UFH requirement
2. Increase dose requirement by 10%-20%
3. Divide dose by 2 for BID dosing
4. D/C IV UFH and administer SC UFH
5. Check heparin assay after 6 hours
6. Adjust dose according to nomogram just
presented
OB Population (3rd Trimester):
Standard Dose: 10,000 units/dose q12hr (sometimes 7,500 units/dose) then adjusted according to labs

Considerations:
Available lab services (aPTT vs. anti-Xa)
Correlation between aPTT and anti-Xa
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