Internal and Emergency Medicine

, Volume 2, Issue 2, pp 76–83 | Cite as

The coagulation system in endocrine disorders: A narrative review

  • A. Squizzato
  • V. E. A. Gerdes
  • W. Ageno
  • H. R. Büller


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.


Coagulation Hypothyroidism Hyperthyroidism Hypercortisolism Growth hormone Bleeding Thrombosis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Orwoll ES, Orwoll RL (1987) Hematologic abnormalities in patients with endocrine and metabolic disorders. Hematol Oncol Clin North Am 1:261–279PubMedGoogle Scholar
  2. 2.
    Rosendaal FR, van Hylckama Vlieg A, Tanis BC, Helmerhorst FM (2003) Estrogens, progestogens and thrombosis. J Thromb Haemost 1:1371–1380PubMedCrossRefGoogle Scholar
  3. 3.
    Winkler UH (1996) Effects of androgens on haemostasis. Maturitas 24:147–155PubMedGoogle Scholar
  4. 4.
    Hartgens F, Kuipers H (2004) Effects of androgenic-anabolic steroids in athletes. Sports Med 34:513–554PubMedCrossRefGoogle Scholar
  5. 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 90:6064–6071PubMedCrossRefGoogle Scholar
  6. 6.
    Hofbauer LC, Heufelder AE (1997) Coagulation disorders in thyroid diseases. Eur J Endocrinol 136:1–7PubMedGoogle Scholar
  7. 7.
    Marongiu F, Cauli C, Mariotti S (2004) Thyroid, hemostasis and thrombosis. J Endocrinol Invest 27:1065–1071PubMedGoogle Scholar
  8. 8.
    Shih CH, Chen SL, Yen CC et al (2004) Thyroid hormone receptor dependent transcriptional regulation of fibrinogen and coagulation proteins. Endocrinology 145:2804–2814PubMedCrossRefGoogle Scholar
  9. 9.
    Ford HC, Carter JM (1990) Haemostasis in hypothyroidism. Postgrad Med J 66:280–284PubMedGoogle Scholar
  10. 10.
    Erem C, Kavgaci H, Ersoz HO et al (2003) Blood coagulation and fibrinolytic activity in hypothyroidism. Int J Clin Pract 57:78–81PubMedGoogle Scholar
  11. 11.
    Dalton RG, Dewar MS, Savidge GF et al (1987) Hypothyroidism as a cause of acquired von Willebrand’s disease. Lancet 1:1007–1009PubMedCrossRefGoogle Scholar
  12. 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 7:113–115PubMedGoogle Scholar
  13. 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 93:392–393PubMedGoogle Scholar
  14. 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 8:142–144PubMedCrossRefGoogle Scholar
  15. 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 89:1346Google Scholar
  16. 16.
    Egeberg BO (1963) Influence of thyroid function on the blood clotting system. Scand J Clin Lab Invest 15:1–7Google Scholar
  17. 17.
    Simone JV, Abildgaard CF, Schulman I (1965) Blood coagulation in thyroid dysfunction. N Engl J Med 273:1057–1061PubMedCrossRefGoogle Scholar
  18. 18.
    Nordoy A, Vikmo H, Berntsen H (1976) Haemostatic and lipid abnormalities in hypothyroidism. Scand J Haematol 16:154–160PubMedCrossRefGoogle Scholar
  19. 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 31:131–137PubMedCrossRefGoogle Scholar
  20. 20.
    Chadaverian R, Bruckert E, Ankri A et al (1998) Relationship between thyroid hormones and plasma D-dimer levels. Thromb Haemost 79:99–103Google Scholar
  21. 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 86:732–737CrossRefGoogle Scholar
  22. 22.
    Erem C, Ersoz H, Karti SS et al (2002) Blood coagulation and fibrinolysis in hyperthyroidism. J Endocrinol Invest 25:345–350PubMedGoogle Scholar
  23. 23.
    Marongiu F, Conti M, Mameli G et al (1988) Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment. J Endocrinol Invest 11:723–725PubMedGoogle Scholar
  24. 24.
    Kellet HA, Sawers JSA, Boulton FE et al (1986) Problems of anticoagulation with warfarin in hyperthyroidism. Q Med J 58:43–51Google Scholar
  25. 25.
    Rogers JS II, Shane SR (1983) Factor VIII activity in normal volunteers receiving oral thyroid hormone. J Lab Clin Med 102:444PubMedGoogle Scholar
  26. 26.
    Squizzato A, Gerdes VE, Brandjes DP et al (2005) Thyroid diseases and cerebrovascular disease. Stroke 36:2302–2310PubMedCrossRefGoogle Scholar
  27. 27.
    Stam J (2005) Thrombosis of the cerebral veins and sinuses. N Engl J Med 352:1791–1798PubMedCrossRefGoogle Scholar
  28. 28.
    Boscaro M, Barzon L, Fallo F, Sonino N (2001) Cushing’s syndrome. Lancet 357:783–791PubMedCrossRefGoogle Scholar
  29. 29.
    La Brocca A, Terzolo M, Pia A et al (1997) Recurrent thromboembolism as a hallmark of Cushing’s syndrome. J Endocrinol Invest 20:211–214PubMedGoogle Scholar
  30. 30.
    Yoshimura S, Ago T, Kitazono T et al (2005) Cerebral sinus thrombosis in a patient with Cushing’s syndrome. J Neurol Neurosurg Psychiatry 76:1182–1183PubMedCrossRefGoogle Scholar
  31. 31.
    Sjoberg HE, Blomback M, Granberg PO (1976) Thromboembolic complications, heparin treatment and increase in coagulation factors in Cushing’s syndrome. Acta Med Scand 199:95–98PubMedCrossRefGoogle Scholar
  32. 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 54:518–520PubMedGoogle Scholar
  33. 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 23:145–150PubMedGoogle Scholar
  34. 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 3:789–793PubMedCrossRefGoogle Scholar
  35. 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 108:294–298PubMedCrossRefGoogle Scholar
  36. 36.
    Boscaro M, Sonino N, Scarda A et al (2002) Anticoagulant prophylaxis markedly reduces thromboembolic complications in Cushing’s syndrome. J Clin Endocrinol Metab 87:3662–3666PubMedCrossRefGoogle Scholar
  37. 37.
    Feuillet L, Guedj E, Laksiri N et al (2004) Deep vein thrombosis after intravenous immunoglobulins associated with methylprednisolone. Thromb Haemost 92:662–665PubMedGoogle Scholar
  38. 38.
    Isacson S (1970) Effect of prednisolone on the coagulation and fibrinolytic systems. Scand J Haematol 7:212–216PubMedCrossRefGoogle Scholar
  39. 39.
    Ozsoylu S, Stauss HS, Diamond LK (1962) Effects of corticosteroids on coagulation of blood. Nature 195:1214–1215PubMedCrossRefGoogle Scholar
  40. 40.
    Jorgensen KA, Sorensen P, Freund L (1982) Effect of glucocorticosteroids on some coagulation test. Acta Haematol 68:39–43PubMedCrossRefGoogle Scholar
  41. 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 68:69–73PubMedGoogle Scholar
  42. 42.
    Muhlfelder TW, Niemetz J, Kang S (1982) Glucocorticoids inhibit the generation of leukocyte procoagulant (tissue factor) activity. Blood 60:1169–1172PubMedGoogle Scholar
  43. 43.
    Lieberman E, Heuser E, Gilchrist GS et al (1968) Thrombosis, nephrosis, and corticosteroid therapy. J Pediatr 73:320–328PubMedCrossRefGoogle Scholar
  44. 44.
    Matusiewicz R, Stempniak M, Lebiedowski K et al (1989) The most frequent complications during long-term corticotherapy. Wiad Lek 42:273–277PubMedGoogle Scholar
  45. 45.
    Cosgriff S (1951) Thromboembolic complications associated with ACTH and cortisone therapy. JAMA 147:924–926Google Scholar
  46. 46.
    Brotman DJ, Girod JP, Posch A et al (2005) Effects of short-term glucocorticoids on hemostatic factors in healthy volunteers. Thromb Res 118:247–252PubMedCrossRefGoogle Scholar
  47. 47.
    Brotman DJ, Girod JP, Garcia MJ et al (2005) Effects of short-term glucocorticoids on cardiovascular biomarkers. J Clin Endocrinol Metab 90:3202–3208PubMedCrossRefGoogle Scholar
  48. 48.
    Derex L, Giraud P, Hanss M et al (1998) Spontaneous intracerebral hemorrhage revealing Addison’s disease. Cerebrovasc Dis 8:240–243PubMedCrossRefGoogle Scholar
  49. 49.
    Asherson RA, Hughes GR (1989) Recurrent deep vein thrombosis and Addison’s disease in “primary” antiphospholipid syndrome. J Rheumatol 16:378–380PubMedGoogle Scholar
  50. 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) 52:123–126CrossRefGoogle Scholar
  51. 51.
    Espinosa G, Cervera R, Font J, Asherson RA (2003) Adrenal involvement in the antiphospholipid syndrome. Lupus 12:569–572PubMedCrossRefGoogle Scholar
  52. 52.
    Vance ML, Mauras N (1999) Growth hormone therapy in adults and children. N Engl J Med 341:1206–1216PubMedCrossRefGoogle Scholar
  53. 53.
    Colao A, Lombardi G (1998) Growth-hormone and prolactin excess. Lancet 352:1455–1461PubMedCrossRefGoogle Scholar
  54. 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 108:486–492PubMedCrossRefGoogle Scholar
  55. 55.
    Rosen T, Bengtsson BA (1990) Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336:285–288PubMedCrossRefGoogle Scholar
  56. 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 105:331–335PubMedCrossRefGoogle Scholar
  57. 57.
    Landin-Wilhelmsen K, Tengborn L, Wilhelmsen L, Bengtsson BA (1997) Elevated fibrinogen levels decrease following treatment of acromegaly. Clin Endocrinol (Oxf) 46:69–74CrossRefGoogle Scholar
  58. 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 76:422–428PubMedGoogle Scholar
  59. 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 51:387–388CrossRefGoogle Scholar
  60. 60.
    Tanriverdi F, Gul A, Eryol NK et al (2005) Massive cardiac thrombosis in a patient with Sheehan’s syndrome. Endocrin J 52:709–714CrossRefGoogle Scholar
  61. 61.
    Wallaschofski H, Donné M, Eigenthaler M et al (2001) PRL as a novel potent cofactor for platelet aggregation. J Clin Endocrinol Metab 86:5912–5919PubMedCrossRefGoogle Scholar
  62. 62.
    Wallaschofski H, Kobsar A, Koksch M et al (2003) Prolactin receptor signaling during platelet activation. Horm Metab Res 35:228–235PubMedCrossRefGoogle Scholar
  63. 63.
    von Kanel R, Dimsdale JE (2000) Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. Eur J Haematol 65:357–369CrossRefGoogle Scholar
  64. 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 9:35–51Google Scholar
  65. 65.
    Biggs R, MacFarlane RG, Philling J (1947) Observations on fibrinolysis. Experimental activity produced by exercise or adrenaline. Lancet 1:405Google Scholar
  66. 66.
    Ingram GIC (1961) Increase in antihemophilic globulin activity following infusion of adrenaline. J Physiol 156:217–224PubMedGoogle Scholar
  67. 67.
    Grant PJ (1990) Hormonal regulation of the acute haemostatic response to stress. Blood Coagul Fibrinolysis 1:299–306PubMedCrossRefGoogle Scholar
  68. 68.
    Shulkin BL, Shapiro B, Sisson JC (1987) Pheochromocytoma, polycythemia, and venous thrombosis. Am J Med 83:773–776PubMedCrossRefGoogle Scholar
  69. 69.
    Stevenson S, Ramani V, Nasim A (2005) Extra-adrenal pheochromocytoma: an unusual cause of deep vein thrombosis. J Vasc Surg 42:570–572PubMedCrossRefGoogle Scholar
  70. 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 15:717–718PubMedCrossRefGoogle Scholar
  71. 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 2:1316–1320PubMedCrossRefGoogle Scholar
  72. 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 95:995–1001PubMedCrossRefGoogle Scholar
  73. 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 32:965–971PubMedGoogle Scholar
  74. 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 51:164–172PubMedCrossRefGoogle Scholar
  75. 75.
    Ganguly A (1998) Primary aldosteronism. N Engl J Med 339:1828–1834PubMedCrossRefGoogle Scholar
  76. 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 45:1243–1248PubMedCrossRefGoogle Scholar
  77. 77.
    Rosendaal FR (1999) Venous thrombosis: a multicausal disease. Lancet 353:1167–1173PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia Srl 2007

Authors and Affiliations

  • A. Squizzato
    • 1
    • 2
  • V. E. A. Gerdes
    • 2
  • W. Ageno
    • 1
  • H. R. Büller
    • 2
  1. 1.Department of Clinical MedicineUniversity of InsubriaVareseItaly
  2. 2.Department of Vascular MedicineAcademic Medical CenterAmsterdamThe Netherlands

Personalised recommendations