Heparin Activity in Systemic Mastocytosis EARL W. CAMPBELL, JR., M.D.; DAVID HECTOR, M.D.; and VEENA GOSSAIN, M.D. Michigan State University School of Medicine; East Lansing, Michigan
SYSTEMIC MASTOCYTOSIS is characterized by mast-cell
infiltration of various organs, particularly dermis and reticuloendothelial systems. The disorder is rare in blacks (1). In children the skin lesions most often disappear spontaneously. The pathognomonic skin lesions are multiple, irregular, reddish-brown macules and papules that urticate when stroked. Benign aspects of the disorder include flushing, itching, and urticaria. Less frequently vomiting, syncope, or shock may occur intermittently. Rare complications include respiratory distress and duodenal ulcer. Mast cells are known to contain histamine and heparin (2, 3). Most symptoms are presumed to be a result of histamine release from mast cells and often coincide with increased urinary excretion of free histamines and metabolities. Histamine can be measured accurately, whereas assessment of heparin has until recently been technically difficult. The availability of the protamine-corrected thrombin-clotting time devised by Penner (4, 5) allows specific determination of heparin effect in plasma. The following case suggests that heparin may reach significant levels during episodes of stress in patients with systemic mastocytosis. An 11-month-old black male child with known systemic mastocytosis was admitted with generalized progressive urticaria. The diagnosis of mastocytosis had been made at birth and confirmed by skin biopsy. The disorder, quiescent until several days 9 4 0
June 1979 • Annals of Internal Medicine • Volume 90 • Number 6
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2. D E M I S J: Mast cell disease, in Clinical Dermatology, Section 4, Unit 4-11, Hagerstown, Maryland, Harper and Row, 1977, pp. 1-27 3. R I L E Y J: Functional significance of histamine and heparin in tissue mast cells. Ann NY Acad Sci 103:151-178, 1963 4. P E N N E R J: Experience with a thrombin clotting time assay for measuring heparin activity. Am J Clin Pathol 61:645-653, 1974 5. P E N N E R J: Blood Coagulation Manual (suppl). Ann Arbor, Michigan, University of Michigan Press, 1975 © 1 9 7 9 American College of Physicians
Figure 1 . Infant at admission. Note appearance of lesions.
before admission, flared during treatment of otitis media with ampicillin (Figure 1). On admission vital signs included regular pulse at 128/s; blood pressure, 130/85 mm Hg; respiratory rate 30/s; and temperature, 38.2 °C. The skin showed generalized dark pigmentation with diffuse, less-pigmented macules and scattered wheals measuring V2 to 1 cm in diameter. Plaquelike confluent urticariae were noted about hands, feet, genitalia, left eyelid, and perioral mucosa. The head, ears, nose, throat, chest, and abdomen were normal, as were neurologic evaluations. The hospital course was complicated by the onset of gastrointestinal hemorrhage during the second hospital day, which did not respond to medical therapy. Enteroscopy and exploratory laparotomy were done. A pyloric channel ulcer was identified, which was treated by vagotomy and pyloroplasty. Biopsies showed significant infiltration of gastric, duodenal, and hepatic tissues with mast cells. Laboratory studies of specific interest included: Day 1: hemoglobin, 10.3 g/dL; hematocrit, 33%; leukocytes, 10 400/mm3 with 3 metamyelocytes, 29 bands, 14 neutrophils, and 5 monocytes. Day 2: (after transfusion) prothrombin time, 10.5 s; accelerated partial thromboplastin time, 34 s; thrombin-clotting time, 13.5 s (control, 7.6 to 8.8 s); protamine-corrected thrombin-clotting time (1.7 heparin units). Day 14: accelerated partial thromboplastin time, 29 s; thrombin-clotting time, 10.7 s; a protamine-corrected thrombin-clotting time (0.1 heparin units); serum histamine, 13 jug/dL (normal, 4 to 7 jug/dL). Day 25: prothrombin time, 12.2 s; accelerated partial thromboplastin time, 22 s; thrombin-clotting time, 10 s; protamine corrected thrombin-clotting time ( < 0.05 heparin units). This case is of interest because of an episode of florid urtication and concomitant gastrointestinal bleeding. Attributing the hemorrhage to a single cause is not possible. However, dilitation of enteric capillaries and gastric secretion enhancement, both known effects of histamine secretion, may have been contributory. Enteric mucosal histamine-releasing lesions may have broken down and ulcerated. A third possibility, elevation of heparin levels to anticoagulant levels, may have contributed significantly to the bleeding. The heparin level, 1.7 U / m L during the acute episode, was near the therapeutic anticoagulant range (2 to 4 heparin units per millilitre of plasma). After restoration of quiescence, the heparin level returned to normal. That the heparin level may have been within the effective anticoagulant range during the early phase of the acute episode before dilution with transfused blood is entirely possible. REFERENCES
1. LANTIS J, KOBLENZER PJ: Solitary mast cell tumor. Arch 99:60-63, 1969
Dermatol Brief Reports
Downloaded From: https://annals.org/ by a University of Texas User on 10/11/2018
941
SYSTEMIC MASTOCYTOSIS is characterized by mast-cell
infiltration of various organs, particularly dermis and reticuloendothelial systems. The disorder is rare in blacks (1). In children the skin lesions most often disappear spontaneously. The pathognomonic skin lesions are multiple, irregular, reddish-brown macules and papules that urticate when stroked. Benign aspects of the disorder include flushing, itching, and urticaria. Less frequently vomiting, syncope, or shock may occur intermittently. Rare complications include respiratory distress and duodenal ulcer. Mast cells are known to contain histamine and heparin (2, 3). Most symptoms are presumed to be a result of histamine release from mast cells and often coincide with increased urinary excretion of free histamines and metabolities. Histamine can be measured accurately, whereas assessment of heparin has until recently been technically difficult. The availability of the protamine-corrected thrombin-clotting time devised by Penner (4, 5) allows specific determination of heparin effect in plasma. The following case suggests that heparin may reach significant levels during episodes of stress in patients with systemic mastocytosis. An 11-month-old black male child with known systemic mastocytosis was admitted with generalized progressive urticaria. The diagnosis of mastocytosis had been made at birth and confirmed by skin biopsy. The disorder, quiescent until several days 9 4 0
June 1979 • Annals of Internal Medicine • Volume 90 • Number 6
Downloaded From: https://annals.org/ by a University of Texas User on 10/11/2018
2. D E M I S J: Mast cell disease, in Clinical Dermatology, Section 4, Unit 4-11, Hagerstown, Maryland, Harper and Row, 1977, pp. 1-27 3. R I L E Y J: Functional significance of histamine and heparin in tissue mast cells. Ann NY Acad Sci 103:151-178, 1963 4. P E N N E R J: Experience with a thrombin clotting time assay for measuring heparin activity. Am J Clin Pathol 61:645-653, 1974 5. P E N N E R J: Blood Coagulation Manual (suppl). Ann Arbor, Michigan, University of Michigan Press, 1975 © 1 9 7 9 American College of Physicians
Figure 1 . Infant at admission. Note appearance of lesions.
before admission, flared during treatment of otitis media with ampicillin (Figure 1). On admission vital signs included regular pulse at 128/s; blood pressure, 130/85 mm Hg; respiratory rate 30/s; and temperature, 38.2 °C. The skin showed generalized dark pigmentation with diffuse, less-pigmented macules and scattered wheals measuring V2 to 1 cm in diameter. Plaquelike confluent urticariae were noted about hands, feet, genitalia, left eyelid, and perioral mucosa. The head, ears, nose, throat, chest, and abdomen were normal, as were neurologic evaluations. The hospital course was complicated by the onset of gastrointestinal hemorrhage during the second hospital day, which did not respond to medical therapy. Enteroscopy and exploratory laparotomy were done. A pyloric channel ulcer was identified, which was treated by vagotomy and pyloroplasty. Biopsies showed significant infiltration of gastric, duodenal, and hepatic tissues with mast cells. Laboratory studies of specific interest included: Day 1: hemoglobin, 10.3 g/dL; hematocrit, 33%; leukocytes, 10 400/mm3 with 3 metamyelocytes, 29 bands, 14 neutrophils, and 5 monocytes. Day 2: (after transfusion) prothrombin time, 10.5 s; accelerated partial thromboplastin time, 34 s; thrombin-clotting time, 13.5 s (control, 7.6 to 8.8 s); protamine-corrected thrombin-clotting time (1.7 heparin units). Day 14: accelerated partial thromboplastin time, 29 s; thrombin-clotting time, 10.7 s; a protamine-corrected thrombin-clotting time (0.1 heparin units); serum histamine, 13 jug/dL (normal, 4 to 7 jug/dL). Day 25: prothrombin time, 12.2 s; accelerated partial thromboplastin time, 22 s; thrombin-clotting time, 10 s; protamine corrected thrombin-clotting time ( < 0.05 heparin units). This case is of interest because of an episode of florid urtication and concomitant gastrointestinal bleeding. Attributing the hemorrhage to a single cause is not possible. However, dilitation of enteric capillaries and gastric secretion enhancement, both known effects of histamine secretion, may have been contributory. Enteric mucosal histamine-releasing lesions may have broken down and ulcerated. A third possibility, elevation of heparin levels to anticoagulant levels, may have contributed significantly to the bleeding. The heparin level, 1.7 U / m L during the acute episode, was near the therapeutic anticoagulant range (2 to 4 heparin units per millilitre of plasma). After restoration of quiescence, the heparin level returned to normal. That the heparin level may have been within the effective anticoagulant range during the early phase of the acute episode before dilution with transfused blood is entirely possible. REFERENCES
1. LANTIS J, KOBLENZER PJ: Solitary mast cell tumor. Arch 99:60-63, 1969
Dermatol Brief Reports
Downloaded From: https://annals.org/ by a University of Texas User on 10/11/2018
941
