1. Heparin-induced skin lesions
Ralf Ludwig, MD
Department of Dermatology
University of Lübeck

2. Heparin-induced skin lesions: Overview
What generated the interest...?
Causes of heparin-induced skin lesions
Incidence of heparin-induced skin lesions
Diagnostic management
Therapeutic management

3. Starting point: Learning from own errow
Patient admitted for venous leg ulcer
Immobilized due to pain
History of „heparin allergy“
Anticoagulation with danaparoid
Contact Derm 49:158 (2003)

4. Starting point: Learning from own errow
Patient admitted for venous leg ulcer
Immobilized due to pain
History of „heparin allergy“
Anticoagulation with danaparoid
Fondaparinux tolerated for 2 weeks
Contact Derm 49:158 (2003)

5. Causes of heparin-induced skin lesions
1. Delayed type hypersensitivity; n>300
2. Cutaneous HIT manifestation; n>20
3. Rare causes; n<10
- Immediate hypersensitivity
- Recall urticaria
- Pustulosis
- Necrosis
- Haemorrhagia
Thromb Haemost 96:611 (2006)

6. Incidence of heparin-induced skin lesions
Thromb Haemost 96:611 (2006)

7. Prospective epidemiological investigation
Heparin > 7 days
Internal medicine patient
Incidence and cause of heparin-induced skin lesions
24 of 320 (7.5%) with heparin-induced skin lesions
All caused by DTH reaction
Test-reaction
87% 9% 4%
CMAJ 181:477 (2009)

8. Further epidemiological investigations
Cohort
Reference
Incidence (%)
Cause
Surgery
Schindewolf et al (in prep)
2.0
DTH
Internal
CMAJ 181:477
7.5
Pregnancy
Thromb Haemost 81:668
<1.0
DTH ?
Pharmacotherapy 19:1013
2.5
NEJM 362:1586
28.9
19.8
Incidence of heparin-induced skin lesions to LMWH

9. Diagnosis of heparin-induced skin lesions
Differentials
DTH
History
Clinical presentation
Exclude HIT (laboratory)
Biopsy & histology
(Allergologic testing)
HIT

10. History: Risk factors for DTH to heparin
Female gender (OR 3.0)
Obesety, BMI > 25 (OR 4.6)
Duration of therapy, > 9 days (OR 5.9)
Pregnacy (?)
LMWH preparation (?)
LMWH
Patients (#)
Skin lesions (#)
Skin lesions (%)
Nadroparin
117 20
17.1
Enoxaparin
204 8
3.9
Fondaparinux
233 1
0.4

11. Histology: CD3 dominated dermal infiltration
H&E
CD3

12. Only s.c. provocation sensitive and specific
Allergy testig -
Only s.c. provocation sensitive and specific
Contact Derm 50:383 (2004)

13. Summary of diagnostic allgorythm
Lancet 380:1867 (2012)

14. Management of heparin-induced skin lesions
Lancet 380:1867 (2012)

15. Management of heparin-induced skin lesions
Lancet 380:1867 (2012)

16. Management of heparin-induced skin lesions
Lancet 380:1867 (2012)

17. Why fondaparinux..? Fondaparinux > 7 days
Internal medicine or surgical patient
Incidence and cause of fondaparinux-induced skin lesions
1 of 231(0.4%) with fondaparinux-induced skin lesions
Caused by DTH reaction
Mayo Clin Proc 85:913 (2010)

18. Patients with RF for allergy
Call for an individulized heparin therapy
J Clin Oncol 223:2130 (2005)
In oncology patients
Patients with RF for allergy
Fondaparinux
< Enoxaparin / Dalteparin
<<< Nadroparin

19. Thanks to Dept. of Dermatology, JW Goethe University, Frankfurt/Main
Manfred Wolter
Wolf-Henning Boehncke
Roland Kaufmann
Division of Angiology, JW Goethe University, Frankfurt/Main
Marc Schindewolf
Edelgard Lindhoff-Last
Red Cross Blood Donor Service, Dessau
Hartmut Kroll