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Heparin-Induced Thrombocytopenia Syndrome Bullous Lesions Treated with Trypsin-Balsam of Peru-Castor Oil Ointment: A Case Study
Case Study
Ms. D was a 79-year-old, morbidly obese (323 lb, 5 feet, 1 inch tall) Caucasian woman with an extensive medical and surgical history that included bilateral knee replacement several years previously. She developed large blisters (bullous skin reaction) that contained sero-sanguineous fluid. The blisters were disseminated over her body but were most prevalent on the arms, anterior upper chest (predominantly above the breasts), and anterior upper and lower legs. A wound ostomy continence (WOC) nurse specialist was consulted to evaluate and offer recommendations for treatment.
History. Ms. D was admitted to a subacute care facility’s critical care unit in the summer of 2003. She was transferred from the acute care setting following a month-long tertiary care hospitalization. Originally, Ms. D was admitted to the tertiary care facility primarily for congestive heart failure that did not respond to medical therapy. Cardiac catheterization revealed severe aortic valve stenosis and cardiomegaly. The patient was referred to cardiac surgery and had an aortic valve replacement (AVR) with a St. Jude mechanical valve. The surgeon had wanted to use a bioprosthetic valve but Ms. D’s body structure required use of a mechanical valve and subsequent requisite lifelong anticoagulation.
Ms. D’s postoperative course was complicated by a prolonged ICU stay for ongoing low cardiac output syndrome. She also developed respiratory failure and required a tracheotomy with mechanical ventilation. She had a Groshong catheter placed for IV therapy. In addition, she developed tachycardia-bradycardia syndrome and required a pacemaker. Subsequently, she developed atrial fibrillation despite cardioversion attempts and pacing efforts.
Because of the mechanical heart valve and the atrial fibrillation, Ms. D was started on intravenous heparin. Within a week, she developed severe thrombocytopenia; heparin-induced thrombocytopenia (HIT) syndrome was suspected. A HIT assay was positive for heparin-induced platelet antibodies. The heparin was discontinued. Unfortunately, gastrointestinal bleeding also complicated Ms. D’s postoperative course. She was started on argatroban to treat the HIT syndrome and required multiple transfusions. Per chart history, Ms. D’s subsequent anticoagulant therapy included enoxaparin sodium (Lovenox, Rhone-Poulenc Rorer Pharmaceuticals, Inc., Collegeville, Pa.) until a final progression to longer-term oral anticoagulation (warfarin). The exact temporal relationship of argatroban, enoxaparin sodium, and warfarin usage was not specified in the chart history (See Discussion).
On transfer to the subacute care facility, Ms. D’s diagnoses were listed as status post aortic valve replacement, sick sinus syndrome, cardiomegaly, status post pacemaker, atrial fibrillation, hypothyroidism, hypertension, hypercholesterolemia, and ventilator-dependent respiratory failure (VDRF). Her allergies were listed as heparin and heparin products.
Ms. D’s admission medications included pantoprazole (Protonix, Wyeth-Ayerst Pharmaceuticals, Philadelphia, Pa.), 40 mg daily; amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals, Philadelphia, Pa.), 200 mg daily; ipratropium and albuterol (Combivent, Boehringer Ingelheim, Ridgefield, Conn.), two puffs every 6 hours; folic acid (folate), one tablet every day; levothyroxine (Synthroid, Knoll Laboratories, Mount Olive, NJ), 100 mcg daily; miconazole cream (Lotrimin, Schering Corporation, Kenilworth, NJ), applied under breasts bilaterally twice daily; warfarin (Coumadin, DuPont Pharma, Wilmington, Del.), 5 mg daily; nystatin powder applied in groin folds twice daily; docusate sodium (Colace, Roberts Pharmaceutical Corp., Eatontown, NJ), 100 mg twice daily; metoclopramide (Reglan, A.H. Robins Company, Richmond, Va.), 10 mg every 6 hours; zinc sulfate, 200 mg daily; iron sulfate, 325 mg every 12 hours; and regular insulin coverage on a sliding scale. Ms. D’s admission laboratory results included a white blood count of 5,200 (normal is 5,000 to 10,000); hemoglobin and hematocrit, 9.5, 27.6, respectively (normal for women is 12 to 15 and 36 to 44, respectively); platelets, 161,000 (normal is 100,000 to 400,000); electrolytes within normal limits; positive HIT antibodies; albumin 1.9 (normal is 3.2 g/dL to 5.0 g/dL); and pre-albumin 21 (normal is 16 mg/dL to 30 mg/dL).
Ms. D’s subsequent course at the subacute care facility’s critical care unit was complicated further. She experienced multiple episodes of congestive heart failure requiring dobutamine (Dobutrex, Eli Lilly and Company, Indianapolis, Ind.), continuing anasarca, and prolonged weaning process from the mechanical ventilator. She received total parenteral nutrition (TPN), had a nasogastric tube for medications, and required intensive nursing care because she could not move in bed or care for herself.
The WOC nurse was consulted on admission to the subacute facility, at which time Ms. D was placed on a bariatric-style bed with a pressure-reducing mattress. She had a 2 cm x 3 cm Stage II sacral pressure ulcer that responded well to hydrocolloid topical therapy (Tegasorb, 3M Healthcare, St. Paul Minn.) and positioning off the pressure ulcer. She also was experiencing fecal incontinence. To protect the skin, dimethicone ointment (Proshield, Healthpoint, Fort Worth, Tex.) was recommended twice daily as needed. A fungal skin infection of the groin folds was being treated with antifungal therapy (mycostatin ointment) twice a day. No other skin lesions were present at the time except for multiple vivid ecchymoses disseminated along the upper and lower extremities and anterior upper chest that appeared following HIT syndrome diagnosis per chart history.
Soon after the initial consultation (within approximately 5 days), Ms. D developed large sero-sanguineous bullous lesions in and immediately adjacent to the areas of the ecchymoses, which attending physicians attributed to HIT syndrome. By the time the WOC nurse was re-consulted, saline-moistened dressings had been ordered and secured with roller gauze or transparent dressings. A few blisters had ruptured because the gauze dressings had unroofed the blisters when removed. No improvement had been documented with this baseline therapy. All open blisters were oozing substantial amounts of serous and sero-sanguineous fluid.
At the initial consult for these new lesions, the WOC nurse assessed several large bullae over the arms and upper chest (see Figure 1). She noted the status of the skin dressed with gauze alone or gauze and transparent dressings and the fragile condition of the surrounding skin. Recommendations for care included: 1) gentle cleansing of blisters with saline at dressing changes; 2) application of trypsin-balsam of Peru-castor oil ointment (Xenaderm, Healthpoint, Fort Worth, Tex.) twice a day for the blisters, then cover with oil emulsion (non-adherent) impregnated gauze dressings; and 3) roller gauze used only to secure dressings as necessary.
The results of the trypsin-balsam of Peru-castor oil ointment treatment were positive. Within 1 week, the open blisters closed and stopped oozing and intact blisters started to shrink in size as the fluid within was reabsorbed (see Figure 2). Another week of treatment resulted in essentially full healing (see Figure 3). Ms. D was able to tell caregivers by gestures that the treatment was not associated with any pain or discomfort. She did not develop any allergic or contact dermatitis reaction. During these 2 weeks, her condition was stable followed by mild improvement. Nurses commented on the ease of use — ointment application was simple, dressings were changed only twice daily, and the patient did not require pain medications. Treatment was continued for a third week to prevent possible regression of the lesions.
Discussion
Heparin-induced thrombocytopenia syndrome is a potentially devastating adverse reaction to the use of heparin anticoagulant therapy. Early recognition is critical to optimal care related to four factors: 1) the widespread and ever-increasing use of heparin; 2) the devastating nature of HIT; 3) HIT’s unpredictability of occurrence; and 4) uncertainty about diagnosis and treatment. Heparin-induced thrombocytopenia syndrome occurrence is likely to increase given the widespread, increased use of heparin — more than 1 trillion units of heparin were administered last year to approximately 12 million patients.1
Heparin-induced thrombocytopenia syndrome (specifically Type II HIT) is a severe immune-mediated drug reaction that can occur in any patient exposed to heparin. Normally after five or more days of administration, patients develop an antibody to heparin’s attachment to the surface of platelets. The platelets become “activated” and the reticulo-endothelial system consumes the activated platelets. A thrombotic state develops as a result of the platelet activation and the generation of pro-coagulant factors.2,3
Treating HIT. Current initial treatment of acute HIT syndrome in the US involves the use of either of two direct thrombin inhibitors (argatroban or lepirudin). Warfarin cannot be used as monotherapy in acute HIT syndrome because it actually can worsen the pro-coagulant state. For longer-term anticoagulation, warfarin can be added to the argatroban or lepirudin therapy once the platelet count has rebounded to normal. Although enoxaparin sodium has been used previously, newer thinking suggests that it is contraindicated in HIT syndrome because of likely cross reactivity with heparin-dependent (IgG) antibodies.4-7
Complications. Many complications can ensue from HIT syndrome, including integumentary sequelae; myocardial infarction, deep vein thrombosis, pulmonary embolism, limb arterial occlusion, cerebrovascular accident, end-organ damage (eg, renal, hepatic, bowel), and skin damage (which can have many varied presentations and degrees of severity from dermatitis type reaction to necrosis) have been noted. Wound healing interventions and time to healing are, of course, variable and depend on the nature of the tissue damage. The mechanisms that ameliorate or worsen the severity of the skin and tissue reactions are not fully understood. The related literature offers a fuller description of the pathomechanisms and dermal manifestations of HIT syndrome and the need for a timely and thorough differential diagnosis.3,8,9
Using trypsin-balsam of Peru-castor oil ointment. A combination of agents in an ointment consisting of trypsin, balsam of Peru, and castor oil was instituted in the client’s care with excellent outcomes. The agent may have been effective in this devastating dermal crisis because of its ability to increase blood flow to areas of application. Balsam of Peru is a capillary bed stimulant and also has a mildly bactericidal action. Castor oil is used to improve epithelialization by reducing epithelial desiccation and aids in pain reduction by insulating exposed nerve endings. Trypsin helps debride eschar and other necrotic tissue; thereby, likely retarding proliferation of local pathogens.10
The rationale for selecting this product for HIT syndrome bullous lesions relates to its physiologic effects and its ability to provide a moist wound healing environment. Because these blisters can be considered partial-thickness wounds and product literature indicates use for this type of wound, the product is considered approved for such use. The lesions would be protected from desiccation, blood supply (along with oxygen and wound healing nutrients) would be increased, and the bactericidal effect would help retard possible wound infection.
Supportive literature. Recent research supports application of this ointment.11 Peripheral blood flow was studied in 10 healthy persons between the ages of 30 and 55 years. Baseline blood flow on the volar surface of the forearm was measured using laser Doppler flux measurement (the product was applied only to specific areas of the forearm and nontreated areas were compared). When the trypsin-balsam of Peru-castor oil ointment was applied to a topical area of 3 cm2, the ointment increased blood flow at 1 hour compared to a control site on the other arm. A statistically significant difference (P <0.01) was noted between treated and untreated arms 3 hours after therapy.
Transepidermal water loss (TEWL) was examined to evaluate the ointment’s efficiency as a moisture barrier. Sixteen healthy participants in a carefully controlled environment had TEWL measured on the volar surfaces of both forearms. Test sites were tape stripped until the TEWL was twice the baseline. The trypsin-balsam of Peru-castor oil ointment was applied to the test area and an unstripped control area on the other arm. When compared, the TEWL values on the treated forearm were better than values on the control arm.
Wound healing was evaluated in 19 healthy subjects of both genders. A YAG laser created a 6-mm single epidermal lesion on the subjects’ right and left forearms. One arm was treated with trypsin-balsam of Peru-castor oil ointment and the other with normal saline. Three research outcomes (erythema, re-epithelialization, and crusting) were followed over 10 days using a scale of 0 to 10 (where 0 = no erythema and 10 = severe erythema; 0 = no scabbing and 10 = severe scabbing; 0 = totally open lesion and 10 = completely healed lesion) Compared to controls, wounds treated with the trypsin-balsam of Peru-castor oil ointment showed significantly (P <0.05) less erythema and greater epithelialization. Significantly less crusting occurred in treatment wounds at days 4, 6, 8, and 10 than the control wounds.
The trypsin-balsam of Peru-castor oil ointment’s potential to initiate either local skin irritation or contact dermatitis was studied in 212 subjects during a three-phase study. Using repeated-insult patch test (RIPT) technique over 3 weeks, researchers demonstrated that no adverse skin reactions were associated with the trypsin-Balsam of Peru-castor oil ointment.11
A recent retrospective, non-controlled study examined the use of the trypsin-Balsam of Peru-castor oil ointment to assist healing skin graft donor sites.12 In the 36 patients treated, all donor sites were epithelialized in 11 days (mean 8 days). No complications occurred and the patients reported comfort with treatments. The authors suggest that the product may have comparable efficacy, better cost-effectiveness, and improved ease of use compared to traditional gauze dressings.
A recent review discussed the trypsin-balsam of Peru-castor oil ointment’s benefits in preventing and treating perineal dermatitis by acting as a moisture barrier and influencing blood flow to areas of affected skin.13 Although the trypsin-balsam of Peru-castor oil ointment’s constituents were previously combined in an aerosol product called Granulex (Bertek, Mylan Bertek Pharmaceuticals, Durham, NC), research comparing the two products demonstrated that the trypsin-balsam of Peru-castor oil ointment was significantly (P <0.5) more effective in healing intentionally created laser wounds in research subjects.13,14
Trypsin-balsam of Peru-castor oil ointment is a new formulation that likely exerts its beneficial effects by increasing blood supply to treated areas. By improving oxygen supply to affected areas, removing carbon dioxide and metabolic wastes, and delivering nutrients to the damaged skin, the ointment optimizes the wound bed environment. As a non-adherent protective covering between the skin and external forces, the ointment protects wounded skin from external moisture, irritants, and infective agents.
Limitations
Several limitations exist in this case study aside from the obvious use of single research subject for treatment. The trypsin-balsam of Peru-castor oil ointment was used with oil emulsion dressings to avoid the potential recurrence of rupturing the blisters with dressing changes. In the future, it may be helpful to treat similar conditions with the trypsin-balsam of Peru-castor oil ointment alone versus the ointment and oil emulsion to assess the possible interactive effects of the ointment with the creation of the moist occlusive environment afforded by the oil emulsion dressing and compare their impact on healing. Generally, no “standard” treatment exists for these lesions to which this approach can be compared; they are partial-thickness blisters and adhesive dressings should be avoided. Like other lesions, expected outcomes include full healing with little discomfort.
Another limitation is the possible interactive effect of anasarca on the HIT lesions. The periodic but continuing generalized edema experienced by the patient may have worsened the bullous lesions manifested by the patient and slowed initial improvement until the trypsin-balsam of Peru-castor oil ointment therapy commenced.
Conclusion
This case study presented an elderly, morbidly obese woman with a highly complex medical and surgical history who developed a HIT syndrome-related dermal reaction. Topical therapy with trypsin-balsam of Peru-castor oil ointment provided prompt, comfortable healing for the patient and ease of use for caregiving staff. The study outcomes suggest that trypsin-balsam of Peru-castor oil ointment is a potential option for other dermal reactions and disorders.
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