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The coagulation system in endocrine disorders: A narrative review

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Abstract

Endocrine disorders can influence the haemostatic balance. Abnormal coagulation test results have been observed in patients with abnormal hormone levels. Also unprovoked bleeding or thrombotic events have been associated with endocrine disease. The aim of the present review is to summarise the available evidence on the influence of common endocrine disorders on the coagulation system, and their possible clinical implications. We focus on thyroid dysfunction, hyper- and hypocortisolism and growth hormone disturbances, while other endocrine disorders are only briefly discussed. In the published literature a clear bleeding diathesis has only been associated with overt hypothyroidism, mainly mediated by an acquired von Willebrand syndrome. A clinically relevant hypercoagulable state may be present in patients with hyperthyroidism, hypercortisolism or abnormal growth hormone levels, but adequate prospective clinical studies are lacking. Also effects of pheochromocytoma, hyperprolactinaemia and hyperaldosteronism on the coagulation system have been described. It is apparent that unprovoked bleeding and thrombotic episodes can be secondary to endocrine disorders.

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References

  1. Orwoll ES, Orwoll RL (1987) Hematologic abnormalities in patients with endocrine and metabolic disorders. Hematol Oncol Clin North Am 1:261–279

    PubMed  CAS  Google Scholar 

  2. Rosendaal FR, van Hylckama Vlieg A, Tanis BC, Helmerhorst FM (2003) Estrogens, progestogens and thrombosis. J Thromb Haemost 1:1371–1380

    Article  PubMed  CAS  Google Scholar 

  3. Winkler UH (1996) Effects of androgens on haemostasis. Maturitas 24:147–155

    PubMed  CAS  Google Scholar 

  4. Hartgens F, Kuipers H (2004) Effects of androgenic-anabolic steroids in athletes. Sports Med 34:513–554

    Article  PubMed  Google Scholar 

  5. Sowers MFR, Jannausch M, Randolph JF et al (2005) Androgens are associated with hemostatic and inflammatory factors among women at the mid-life. J Clin Endocrinol Metab 90:6064–6071

    Article  PubMed  CAS  Google Scholar 

  6. Hofbauer LC, Heufelder AE (1997) Coagulation disorders in thyroid diseases. Eur J Endocrinol 136:1–7

    PubMed  CAS  Google Scholar 

  7. Marongiu F, Cauli C, Mariotti S (2004) Thyroid, hemostasis and thrombosis. J Endocrinol Invest 27:1065–1071

    PubMed  CAS  Google Scholar 

  8. Shih CH, Chen SL, Yen CC et al (2004) Thyroid hormone receptor dependent transcriptional regulation of fibrinogen and coagulation proteins. Endocrinology 145:2804–2814

    Article  PubMed  CAS  Google Scholar 

  9. Ford HC, Carter JM (1990) Haemostasis in hypothyroidism. Postgrad Med J 66:280–284

    PubMed  CAS  Google Scholar 

  10. Erem C, Kavgaci H, Ersoz HO et al (2003) Blood coagulation and fibrinolytic activity in hypothyroidism. Int J Clin Pract 57:78–81

    PubMed  CAS  Google Scholar 

  11. Dalton RG, Dewar MS, Savidge GF et al (1987) Hypothyroidism as a cause of acquired von Willebrand’s disease. Lancet 1:1007–1009

    Article  PubMed  CAS  Google Scholar 

  12. Michiels JJ, Schroyens W, Berneman Z, van der Planken M (2001) Acquired von Willebrand syndrome 1 in hypothyroidism: reversal after treatment with thyroxine. Clin Appl Thromb Hemost 7:113–115

    PubMed  CAS  Google Scholar 

  13. Franchini M, Veneri D, Lippi G (2005) Analysis of thyroid hormone status in 131 consecutive individuals with low von Willebrand factor levels. Thromb Haemost 93:392–393

    PubMed  CAS  Google Scholar 

  14. Franchini M, De Gironcoli M, Lippi G et al (2002) Efficacy of desmopressin as surgical prophylaxis in patients with acquired von Willebrand disease undergoing thyroid surgery. Haemophilia 8:142–144

    Article  PubMed  CAS  Google Scholar 

  15. Franchini M, Zugni C, Veneri D et al (2004) High prevalence of acquired von Willebrand’s syndrome in patients with thyroid diseases undergoing thyroid surgery. Haematologica 89:1346

    Google Scholar 

  16. Egeberg BO (1963) Influence of thyroid function on the blood clotting system. Scand J Clin Lab Invest 15:1–7

    Google Scholar 

  17. Simone JV, Abildgaard CF, Schulman I (1965) Blood coagulation in thyroid dysfunction. N Engl J Med 273:1057–1061

    Article  PubMed  CAS  Google Scholar 

  18. Nordoy A, Vikmo H, Berntsen H (1976) Haemostatic and lipid abnormalities in hypothyroidism. Scand J Haematol 16:154–160

    Article  PubMed  CAS  Google Scholar 

  19. Muller B, Tsakiris DA, Roth CB et al (2001) Haemostatic profile in hypothyroidism as potential risk for vascular or thrombotic disease. Eur J Clin Invest 31:131–137

    Article  PubMed  CAS  Google Scholar 

  20. Chadaverian R, Bruckert E, Ankri A et al (1998) Relationship between thyroid hormones and plasma D-dimer levels. Thromb Haemost 79:99–103

    Google Scholar 

  21. Chadaverian R, Bruckert E, Leenhardt L et al (2001) Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism. J Clin Endocrinol Metab 86:732–737

    Article  Google Scholar 

  22. Erem C, Ersoz H, Karti SS et al (2002) Blood coagulation and fibrinolysis in hyperthyroidism. J Endocrinol Invest 25:345–350

    PubMed  CAS  Google Scholar 

  23. Marongiu F, Conti M, Mameli G et al (1988) Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment. J Endocrinol Invest 11:723–725

    PubMed  CAS  Google Scholar 

  24. Kellet HA, Sawers JSA, Boulton FE et al (1986) Problems of anticoagulation with warfarin in hyperthyroidism. Q Med J 58:43–51

    Google Scholar 

  25. Rogers JS II, Shane SR (1983) Factor VIII activity in normal volunteers receiving oral thyroid hormone. J Lab Clin Med 102:444

    PubMed  CAS  Google Scholar 

  26. Squizzato A, Gerdes VE, Brandjes DP et al (2005) Thyroid diseases and cerebrovascular disease. Stroke 36:2302–2310

    Article  PubMed  CAS  Google Scholar 

  27. Stam J (2005) Thrombosis of the cerebral veins and sinuses. N Engl J Med 352:1791–1798

    Article  PubMed  CAS  Google Scholar 

  28. Boscaro M, Barzon L, Fallo F, Sonino N (2001) Cushing’s syndrome. Lancet 357:783–791

    Article  PubMed  CAS  Google Scholar 

  29. La Brocca A, Terzolo M, Pia A et al (1997) Recurrent thromboembolism as a hallmark of Cushing’s syndrome. J Endocrinol Invest 20:211–214

    PubMed  Google Scholar 

  30. Yoshimura S, Ago T, Kitazono T et al (2005) Cerebral sinus thrombosis in a patient with Cushing’s syndrome. J Neurol Neurosurg Psychiatry 76:1182–1183

    Article  PubMed  CAS  Google Scholar 

  31. Sjoberg HE, Blomback M, Granberg PO (1976) Thromboembolic complications, heparin treatment and increase in coagulation factors in Cushing’s syndrome. Acta Med Scand 199:95–98

    Article  PubMed  CAS  Google Scholar 

  32. Patrassi GM, Dal Bo Zanon R, Boscaro M et al (1985) Further studies on the hypercoagulable state of patients with Cushing’s syndrome. Thromb Haemost 54:518–520

    PubMed  CAS  Google Scholar 

  33. Fatti LM, Bottasso B, Invitti C et al (2000) Markers of activation of coagulation and fibrinolysis in patients with Cushing’s syndrome. J Endocrinol Invest 23:145–150

    PubMed  CAS  Google Scholar 

  34. Patrassi GM, Sartori MT, Viero ML et al (1992) The fibrinolytic potential in patients with Cushing’s disease: a clue to their hypercoagulable state. Blood Coagul Fibrinolysis 3:789–793

    Article  PubMed  CAS  Google Scholar 

  35. Ambrosi B, Sartorio A, Pizzocaro A et al (2000) Evaluation of haemostatic and fibrinolytic markers in patients with Cushing’s syndrome and in patients with adrenal incidentaloma. Exp Clin Endocrinol Diabetes 108:294–298

    Article  PubMed  CAS  Google Scholar 

  36. Boscaro M, Sonino N, Scarda A et al (2002) Anticoagulant prophylaxis markedly reduces thromboembolic complications in Cushing’s syndrome. J Clin Endocrinol Metab 87:3662–3666

    Article  PubMed  CAS  Google Scholar 

  37. Feuillet L, Guedj E, Laksiri N et al (2004) Deep vein thrombosis after intravenous immunoglobulins associated with methylprednisolone. Thromb Haemost 92:662–665

    PubMed  CAS  Google Scholar 

  38. Isacson S (1970) Effect of prednisolone on the coagulation and fibrinolytic systems. Scand J Haematol 7:212–216

    Article  PubMed  CAS  Google Scholar 

  39. Ozsoylu S, Stauss HS, Diamond LK (1962) Effects of corticosteroids on coagulation of blood. Nature 195:1214–1215

    Article  PubMed  CAS  Google Scholar 

  40. Jorgensen KA, Sorensen P, Freund L (1982) Effect of glucocorticosteroids on some coagulation test. Acta Haematol 68:39–43

    Article  PubMed  CAS  Google Scholar 

  41. van Giezen JJ, Jansen JW (1992) Inhibition of fibrinolytic activity in vivo by dexamethasone is counterbalanced by an inhibition of platelet aggregation. Thromb Haemost 68:69–73

    PubMed  Google Scholar 

  42. Muhlfelder TW, Niemetz J, Kang S (1982) Glucocorticoids inhibit the generation of leukocyte procoagulant (tissue factor) activity. Blood 60:1169–1172

    PubMed  CAS  Google Scholar 

  43. Lieberman E, Heuser E, Gilchrist GS et al (1968) Thrombosis, nephrosis, and corticosteroid therapy. J Pediatr 73:320–328

    Article  PubMed  CAS  Google Scholar 

  44. Matusiewicz R, Stempniak M, Lebiedowski K et al (1989) The most frequent complications during long-term corticotherapy. Wiad Lek 42:273–277

    PubMed  CAS  Google Scholar 

  45. Cosgriff S (1951) Thromboembolic complications associated with ACTH and cortisone therapy. JAMA 147:924–926

    CAS  Google Scholar 

  46. Brotman DJ, Girod JP, Posch A et al (2005) Effects of short-term glucocorticoids on hemostatic factors in healthy volunteers. Thromb Res 118:247–252

    Article  PubMed  CAS  Google Scholar 

  47. Brotman DJ, Girod JP, Garcia MJ et al (2005) Effects of short-term glucocorticoids on cardiovascular biomarkers. J Clin Endocrinol Metab 90:3202–3208

    Article  PubMed  CAS  Google Scholar 

  48. Derex L, Giraud P, Hanss M et al (1998) Spontaneous intracerebral hemorrhage revealing Addison’s disease. Cerebrovasc Dis 8:240–243

    Article  PubMed  CAS  Google Scholar 

  49. Asherson RA, Hughes GR (1989) Recurrent deep vein thrombosis and Addison’s disease in “primary” antiphospholipid syndrome. J Rheumatol 16:378–380

    PubMed  CAS  Google Scholar 

  50. Satta MA, Corsello SM, Della Casa S et al (2000) Adrenal insufficiency as the first clinical manifestation of the primary antiphospholipid antibody syndrome. Clin Endocrinol (Oxf) 52:123–126

    Article  CAS  Google Scholar 

  51. Espinosa G, Cervera R, Font J, Asherson RA (2003) Adrenal involvement in the antiphospholipid syndrome. Lupus 12:569–572

    Article  PubMed  CAS  Google Scholar 

  52. Vance ML, Mauras N (1999) Growth hormone therapy in adults and children. N Engl J Med 341:1206–1216

    Article  PubMed  CAS  Google Scholar 

  53. Colao A, Lombardi G (1998) Growth-hormone and prolactin excess. Lancet 352:1455–1461

    Article  PubMed  CAS  Google Scholar 

  54. Sartorio A, Cattaneo M, Bucciarelli P et al (2000) Alterations of haemostatic and fibrinolytic markers in adult patients with growth hormone deficiency and with acromegaly. Exp Clin Endocrinol Diabetes 108:486–492

    Article  PubMed  CAS  Google Scholar 

  55. Rosen T, Bengtsson BA (1990) Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336:285–288

    Article  PubMed  CAS  Google Scholar 

  56. Wildbrett J, Hanefeld M, Fucker K et al (1997) Anomalies of lipoprotein pattern and fibrinolysis in acromegalic patients: relation to growth hormone levels and insulin-like growth factor I. Exp Clin Endocrinol Diabetes 105:331–335

    Article  PubMed  CAS  Google Scholar 

  57. Landin-Wilhelmsen K, Tengborn L, Wilhelmsen L, Bengtsson BA (1997) Elevated fibrinogen levels decrease following treatment of acromegaly. Clin Endocrinol (Oxf) 46:69–74

    Article  CAS  Google Scholar 

  58. Johansson JO, Landin K, Johannsson G et al (1996) Longterm treatment with growth hormone decreases plasminogen activator inhibitor-1 and tissue plasminogen activator in growth hormone-deficient adults. Thromb Haemost 76:422–428

    PubMed  CAS  Google Scholar 

  59. Ishizu A, Shimizu C, Tsuji T et al (2004) Peripheral pulmonary embolism related to a thrombus of the inferior vena cava triggering fatal adrenal crisis in Sheehan’s syndrome. Endocrin J 51:387–388

    Article  Google Scholar 

  60. Tanriverdi F, Gul A, Eryol NK et al (2005) Massive cardiac thrombosis in a patient with Sheehan’s syndrome. Endocrin J 52:709–714

    Article  Google Scholar 

  61. Wallaschofski H, Donné M, Eigenthaler M et al (2001) PRL as a novel potent cofactor for platelet aggregation. J Clin Endocrinol Metab 86:5912–5919

    Article  PubMed  CAS  Google Scholar 

  62. Wallaschofski H, Kobsar A, Koksch M et al (2003) Prolactin receptor signaling during platelet activation. Horm Metab Res 35:228–235

    Article  PubMed  CAS  Google Scholar 

  63. von Kanel R, Dimsdale JE (2000) Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. Eur J Haematol 65:357–369

    Article  Google Scholar 

  64. Vosburgh CH, Richards AN (1903) An experimental study of the sugar content and extra vascular coagulation of the blood after administration of adrenalin. Am J Physiol 9:35–51

    CAS  Google Scholar 

  65. Biggs R, MacFarlane RG, Philling J (1947) Observations on fibrinolysis. Experimental activity produced by exercise or adrenaline. Lancet 1:405

    Google Scholar 

  66. Ingram GIC (1961) Increase in antihemophilic globulin activity following infusion of adrenaline. J Physiol 156:217–224

    PubMed  CAS  Google Scholar 

  67. Grant PJ (1990) Hormonal regulation of the acute haemostatic response to stress. Blood Coagul Fibrinolysis 1:299–306

    Article  PubMed  CAS  Google Scholar 

  68. Shulkin BL, Shapiro B, Sisson JC (1987) Pheochromocytoma, polycythemia, and venous thrombosis. Am J Med 83:773–776

    Article  PubMed  CAS  Google Scholar 

  69. Stevenson S, Ramani V, Nasim A (2005) Extra-adrenal pheochromocytoma: an unusual cause of deep vein thrombosis. J Vasc Surg 42:570–572

    Article  PubMed  Google Scholar 

  70. Stella P, Bignotti G, Zerbi S et al (2000) Concurrent pheochromocytoma, diabetes insipidus and cerebral venous thrombosis—a possible unique pathophysiological mechanism. Nephrol Dial Transplant 15:717–718

    Article  PubMed  CAS  Google Scholar 

  71. Hoppener MR, Kraaijenhagen RA, Hutten BA et al (2004) Beta-receptor blockade decreases elevated plasma levels of factor VIII:C in patients with deep vein thrombosis. J Thromb Haemost 2:1316–1320

    Article  PubMed  CAS  Google Scholar 

  72. Vaughan DE, Lazos SA, Tong K (1995) Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. J Clin Invest 95:995–1001

    Article  PubMed  CAS  Google Scholar 

  73. Brown NJ, Agirbasli MA, Williams GH et al (1998) Effect of activation and inhibition of the renin angiotensin system on plasma PAI-1 in humans. Hypertension 32:965–971

    PubMed  CAS  Google Scholar 

  74. Oikawa T, Freeman M, Lo W et al (1997) Modulation of plasminogen activator inhibitor-1 in vivo: a new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition. Kidney Int 51:164–172

    Article  PubMed  CAS  Google Scholar 

  75. Ganguly A (1998) Primary aldosteronism. N Engl J Med 339:1828–1834

    Article  PubMed  CAS  Google Scholar 

  76. Milliez P, Girerd X, Plouin PF et al (2005) Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 45:1243–1248

    Article  PubMed  CAS  Google Scholar 

  77. Rosendaal FR (1999) Venous thrombosis: a multicausal disease. Lancet 353:1167–1173

    Article  PubMed  CAS  Google Scholar 

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Squizzato, A., Gerdes, V.E.A., Ageno, W. et al. The coagulation system in endocrine disorders: A narrative review. Int Emergency Med 2, 76–83 (2007). https://doi.org/10.1007/s11739-007-0026-X

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