When a storm showers the blood clots: a case of thyroid storm with systemic thromboembolism

in Endocrinology, Diabetes & Metabolism Case Reports
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  • 1 Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
  • 2 Department of Haematology, Singapore General Hospital, Singapore, Singapore
  • 3 Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore

Correspondence should be addressed to A C Maung; Email: chanmaung.aye@mohh.com.sg

Summary

Thyroid storm is a rare but potentially life-threatening complication of excessive thyroid hormone action. It is associated with a hypercoagulable state and reported to increase the risk of thromboembolism. However, the role of anticoagulation in thyroid storm still remains controversial and inconclusive. A 22-year-old male with no significant past medical history presented with acute severe generalised abdominal pain. He was found to be profoundly thyrotoxic on arrival at our institution and subsequently diagnosed with thyroid storm secondary to newly diagnosed Graves’ disease. Extensive thromboses of the splanchnic, iliac, femoral veins and pulmonary arteries were subsequently demonstrated on CT scan. He had prolonged bowel ileus as a sequela of mesenteric ischaemia requiring total parenteral nutrition and non-oral forms of anti-thyroid drugs for management of hyperthyroidism. He was in sinus rhythm throughout his inpatient stay, and there was no personal history of prothrombotic conditions. His thrombophilia screen was normal. He eventually required jejunectomy due to jejunal ischaemia from extensive involvement of portal and mesenteric veins. He underwent radioiodine ablation for definitive treatment. He is currently hypothyroid and receiving thyroxine replacement. Thyroid storms are hypercoagulable states and can be associated with extensive thromboembolism even in the absence of atrial fibrillation. To our knowledge, this is the first report of severe extensive thromboembolism complicated by severe mesenteric ischaemia and bowel ileus in the setting of a thyroid storm. Routine prophylactic anticoagulation should be considered in those presenting with thyroid storms.

Learning points

Abstract

Summary

Thyroid storm is a rare but potentially life-threatening complication of excessive thyroid hormone action. It is associated with a hypercoagulable state and reported to increase the risk of thromboembolism. However, the role of anticoagulation in thyroid storm still remains controversial and inconclusive. A 22-year-old male with no significant past medical history presented with acute severe generalised abdominal pain. He was found to be profoundly thyrotoxic on arrival at our institution and subsequently diagnosed with thyroid storm secondary to newly diagnosed Graves’ disease. Extensive thromboses of the splanchnic, iliac, femoral veins and pulmonary arteries were subsequently demonstrated on CT scan. He had prolonged bowel ileus as a sequela of mesenteric ischaemia requiring total parenteral nutrition and non-oral forms of anti-thyroid drugs for management of hyperthyroidism. He was in sinus rhythm throughout his inpatient stay, and there was no personal history of prothrombotic conditions. His thrombophilia screen was normal. He eventually required jejunectomy due to jejunal ischaemia from extensive involvement of portal and mesenteric veins. He underwent radioiodine ablation for definitive treatment. He is currently hypothyroid and receiving thyroxine replacement. Thyroid storms are hypercoagulable states and can be associated with extensive thromboembolism even in the absence of atrial fibrillation. To our knowledge, this is the first report of severe extensive thromboembolism complicated by severe mesenteric ischaemia and bowel ileus in the setting of a thyroid storm. Routine prophylactic anticoagulation should be considered in those presenting with thyroid storms.

Learning points

Background

Thyroid storm is a severe life-threatening complication of decompensated hyperthyroidism. It is associated with a high mortality rate even with appropriate medical therapy. Hyperthyroidism in itself is known to be a hypercoagulable state with previous reports of associated thromboembolic events, usually at a single site. In this report, we describe a young man presenting with thyroid storm and disseminated systemic thromboembolism. To our knowledge, this is the first report of severe extensive thromboembolism complicated by severe mesenteric ischaemia and bowel ileus in the setting of a thyroid storm.

Case presentation

A 22-year-old seaman presented to the Accident and Emergency (A&E) Department with severe central abdominal pain and multiple episodes of vomiting for 9 days. He did not have any significant past medical history. He had lost 6 kg in the last 3 months despite a good appetite. He reported occasional palpitations. He did not experience any tremors of the hands, insomnia, frequency of bowel movements and lower extremity weakness. He had not been taking any medicine or supplements regularly and had no significant family history of thyroid disease. He was a lifelong non-smoker.

En route to A&E, he was noted to be tachycardic (heart rate 180–190 b.p.m.). On arrival, he was febrile (38.6°C), hypotensive (blood pressure (BP) 86/55 mmHg) with sinus tachycardia (heart rate (HR) 190 b.p.m.), oxygen saturation of 98% on room air and breathing at respiration rate of 30 breaths per minute. On examination, he was very agitated, restless and profoundly dehydrated. His Glasgow Coma Score was 15, fully oriented to time, place and person. He was clinically thyrotoxic with bilateral hand tremors and sweaty palms, and was noted to have exophthalmos and lid lag. There was a moderately enlarged diffuse goitre with the presence of thyroid bruit. There was no pretibial myxedema. Cardiovascular and respiratory examinations were normal other than tachycardia. Abdominal examination revealed generalised tenderness with guarding, particularly over the epigastrium. His bowel sounds were reduced.

Investigations and treatment

An ECG revealed sinus tachycardia with HR 196 b.p.m. Thyroid function tests (TFTs) confirmed hyperthyroidism with an elevated FreeT4 (FT4) 66.2 (8.8–14.4 pmol/L) and suppressed TSH <0.010 (0.65–3.70 mU/L) (Table 1). TSH receptor antibody level was positive (6.23 UL/L (<1.76 IU/L)), consistent with Graves’ disease. His calculated Burch and Wartofsky Point Scale (BWPS) score was 60. Thyroid storm was diagnosed based on the above findings and he was subsequently admitted to the Medical High Dependency Unit (HDU). Other investigations revealed acute renal impairment and a markedly raised lactate level of 8.3 (0.5–2.2 mmol/L).

Table 1

Initial investigations done at A&E (abnormal results highlighted in bold).

InvestigationResultReference range
Thyroid function test
 FT4, pmol/L66.28.8–14.4
 FT3, pmol/L10.6 3.2–5.3
 TSH, mU/L<0.0100.65–3.70
Full blood count
 Haemoglobin, g/dL15.814–18
 Total WBC, × 10⁹/L23.684–10
 Platelets, × 10⁹/L258140–440
 Neutrophil absolute, × 10⁹/L17.12–7.5
Renal panel
 Urea, mmol/L10.82.7–6.9
 Sodium, mmol/L142136–146
 Potassium, mmol/L3.9100–107
 Chloride, mmol/L963.9–11
 Bicarbonate, mmol/L21.919–29
 Glucose, mmol/L6.33.6–5.0
 Creatinine, µmol/L22154–101
 Lactate, mmol/L8.30.5–2.2
Liver panel
 Protein, g/L7668–85
 Albumin, g/L3940–51
 Bilirubin, µmol/L387–32
 ALP, U/L11439–99
 ALT, U/L426–66
 AST, U/L2512–42
Coagulation profile
 APTT, s24.625.7–32.9
 PT, s11.59.9–11.4

FT3, free T3; FT4, free T4.

As his abdomen was very tender with signs of guarding, parenteral formulations were used. Rectal PTU (400 mg) was administered as a loading dose followed by 200 mg every 6 h as a fleet enema. IV Sodium Iodide 1 g (containing 850 mg of iodine) was also given 1 h after rectal PTU administration, and continued at a dose of 1 g for every 12 h. IV hydrocortisone 200 mg was started and continued at 100 mg every 8 hours. In view of persistent tachycardia, iv esmolol infusion was initiated to maintain his heart rate below 100 b.p.m.

An initial plain abdomen and pelvis CT was done on the first day of admission showed significant distension of the duodenum, stomach, oesophagus, and a long segment of circumferential mural thickening of jejunal loops associated with dilatation and oedema, suggestive of jejunitis (Fig. 1). A nasogastric tube (NGT) was inserted for intermittent suctioning and bowel rest and 1 L of dark greenish watery gastric juice was aspirated. He was also empirically treated with iv ceftriaxone and iv metronidazole to cover for intrabdominal source of sepsis.

Figure 1
Figure 1

Plain CT AP showing significant gastric distension (red arrow) and fat stranding around jejunum (white arrows).

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2021, 1; 10.1530/EDM-20-0118

By day 4, free T3 levels had normalised (Table 2). The dose of both iv hydrocortisone and sodium iodide were gradually tapered and discontinued. However, he had persistent bowel ileus, and rectal PTU was, therefore, continued. On day 4, he had large episodes of melaena with a fall in haemoglobin level from 9.7 to 8.3 g/dL. This was treated conservatively with intravenous esomperazole and bleeding ceased within 24 h.

Table 2

Trend of TFT with treatment given inpatient (abnormal results highlighted in bold).

RRDay 1Day 2Day 3Day 4Day 5Day 6Day 7Day 13Day 24
FT3, pmol/L3.2–5.314.410.67.15.14.94.63.95.24.9
FT4, pmol/L8.8–14.456.166.264.131.810
TSH, mU/L0.65–3.70<0.010<0.010
TR Ab, IU/L<1.766.23
Rx given
 IV HCT100 mg Q8H100 mg Q8H50 mg Q8H25 mg Q8HSTOPPED
 IV Na Iodide1000 mg Q12H1000 mg Q12H1000 mg Q12H500 mg Q12H500 mg Q12H500 mg Q12HSTOPPED
 Rectal PTU 200 mg Q6H200 mg Q8H100 mg Q8H till day 29

HCT, hydrocortisone; RR, reference range.

Despite the improvement in free T3 levels and broad-spectrum antibiotics, he continued to be febrile (38.4–38.9°C). Cultures of blood and urine did not grow any organisms and another CT scan (with contrast) of the abdomen and pelvis was ordered to look for occult sources of infection. This revealed extensive thrombosis involving the portal and superior mesenteric veins causing mesenteric ischaemia and right external iliac, common femoral vein thrombosis with left lower lobe pulmonary embolism (Fig. 2).

Figure 2
Figure 2

Contrasted CT scan images showing a filling defect in left pulmonary artery (left) and extensive portal vein thrombosis (right).

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2021, 1; 10.1530/EDM-20-0118

As he had a recent episode of melaena, he underwent an oesophagogastroduodenoscopy (OGDS) to exclude a source of active bleeding before anticoagulation was initiated. OGDS showed evidence of pangastritis but no ulcers or active bleeding. Intravenous unfractionated heparin (UFH) infusion was started in view of its shorter half-life and complete reversal with protamine sulphate (1). This was continued for 48 h before switching to subcutaneous enoxaparin 90 mg BD (1 mg/kg twice daily dosing).

In evaluation for thrombophilia, protein C and S levels were not assessed since they were expected to be decreased in the acute thrombotic phase and the initiation of anticoagulation would have interfered with anti-thrombin III measurements. Factor V Leiden and prothrombin gene mutations are not routinely evaluated in Asian populations since the prevalence of mutations in these genes are typically low in this group (2). Given the unusual site of thromboses, causes of acquired thrombophilia were evaluated, including lupus anticoagulant, anticardiolipin IgG, IgM, JAK2 mutation, and paroxysmal noctural haemoglobinuria. These were all negative.

He continued to have prolonged bowel ileus, and was commenced on total parenteral nutrition 1 week after admission. A CT mesenteric angiogram done 13 days later showed interval improvement in the ischaemic jejunal segments with the decrease in clot burden in portomesenteric venous system. Multiple trials of clear feeds orally were attempted once his abdominal ileus improved. However, he was not able to tolerate this with frequent episodes of vomiting. Rectal PTU had to be continued. Bowel ileus gradually improved 5 weeks after his admission and hence rectal PTU was switched to oral carbimazole 20 mg. His TFTs trend and treatment given are summarised in Table 2. Throughout his admission, he remained in sinus rhythm.

Outcome and follow-up

He was discharged after 5 weeks of hospitalisation. He continued to have recurrent abdominal pain, however, and was admitted to a hospital in his home town and underwent a jejunectomy 2 weeks later. Subsequently, he underwent radioiodine (RAI) therapy for definitive treatment of Graves disease. Three weeks after receiving RAI, he was started on levothyroxine 50 µg OM. He is currently taking levothyroxine 75 µg OM and rivaroxaban 15 mg OM.

Discussion

Hyperthyroidism in itself results in an increased risk of major thromboembolism due to an imbalance between the coagulation and fibrinolytic systems (3). Procoagulant mechanisms proposed including increased coagulation cascade from higher plasma levels of factor VIII, IX, von Willebrand factor, fibrinogen, reduced fibrinolytic activity due to lower plasma levels of plasminogen, tissue plasminogen activator and endothelial dysfunction (4, 5, 6, 7). A shortened APTT has been observed as a risk factor for venous thrombosis in hyperthyroidism (8). Notably, our patient also had shortened APTT of 24.6 s. The prevalence of thromboembolism in hyperthyroid patients has reported to be around 8–10% (9). Common sites for thromboembolism include pulmonary embolism and deep venous thrombosis of the lower limbs (10, 11). Cerebral venous thrombosis has also been reported in hyperthyroidism (12). In a nation-wide longitudinal study over 5 years which included 8903 individuals with hyperthyroidism in Taiwan, there was a 2.3-fold increased risk of pulmonary embolism (PE) in patients with hyperthyroidism than in the comparison cohort after adjusting for potential cofounders (11).

The existing data on the role and clinical impact of anticoagulation in hyperthyroidism or thyroid storm-related atrial fibrillation (AF) is inconclusive. Current guidelines would recommend anticoagulation based on CHA2DS2-VASc risk factors which do not include hyperthyroidism (13). However, the risk for developing a stroke was 1.4-fold greater in the hyperthyroid individuals compared with euthyroid controls, even after adjusting for several confounders including age, presence of atrial fibrillation, hypertension, diabetes (14). Hyperthyroidism-associated atrial fibrillation has also been reported to be an independent risk factor for thromboembolism irrespective of CHA2DS2-VASc score (15). Therefore, in the context of hyperthyroidism/thyroid-storm associated AF, anticoagulation should be considered irrespective of the CHA2DS2-VASc score.

There is less clarity whether individuals with severe hyperthyroidism/thyroid storm, but who remain in sinus rhythm, should receive anticoagulation. The level of FT4 in itself appears related to thromboembolic risk (16), with a higher level of FT4 portending higher risk. Nevertheless, majority of hyperthyroid individuals in the community do not present with thromboembolic events and initiating anticoagulation in ambulant hyperthyroid individuals would not be necessary. In considering the three pathophysiological mechanisms (Virchow’s triad) leading to the formation of thrombus: damage to the endothelial wall, venous stasis and hypercoagulability, a state of thyroid storm which represents decompensated hyperthyroidism would be expected increase immobility and hence venous stasis and hypercoagulability from hypovolaemia. This, together with a markedly elevated FT4 would have greatly increased the risk of extensive thromboses in our individual. This highlights the importance on individualised decision making in the context of each patient’s presentation and after weighing the risk vs benefits of anticoagulation.

Conclusion

Thyroid storm is a life-threatening syndrome characterised by exaggerated clinical manifestations of thyrotoxicosis and a state of decompensation. It also presents a hypercoagulable state with an increased risk of thromboembolism. Current guidance on the use of anticoagulation in hyperthyroid states should perhaps be reviewed to extend the use of prophylactic doses of anticoagulation in thyroid storms even in the absence of atrial fibrillation.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

This work did not receive any specific grant from any funding agency in the public, commercial or not for profit sector.

Patient consent

Written informed consent was obtained from the patient for publication of the submitted article and accompanying images.

Author contribution statement

Aye Chan Maung wrote the manuscript. Daphne Su-Lyn Gardner edited the manuscript. All authors attended on the patient and were actively involved in the care of thpatient and reviewed the manuscript.

References

  • 1

    Hirsh J, Anand SS, Halperin JL, Fuster VAmerican Heart Association. Guide to anticoagulant therapy: heparin: a statement for healthcare professionals from the American Heart Association. Circulation 2001 103 29943018. (https://doi.org/10.1161/01.cir.103.24.2994)

    • Search Google Scholar
    • Export Citation
  • 2

    Lee LH, Liu TC, Kuperan P, Tan LK, Tan D, Poon ML, Ong KH, Fong SZ, Tan MY & Ng HJ Hereditary thrombophilia in an unselected cohort of venous thrombosis patients in Singapore. Journal of Clinical Pathology 2011 64 814817. (https://doi.org/10.1136/jclinpath-2011-200018)

    • Search Google Scholar
    • Export Citation
  • 3

    Franchini M Hemostatic changes in thyroid diseases: haemostasis and thrombosis. Hematology 2006 11 20320 8. (https://doi.org/10.1080/10245330600667591)

    • Search Google Scholar
    • Export Citation
  • 4

    Rogers JS, Shane SR & Jencks FS Factor VIII activity and thyroid function. Annals of Internal Medicine 1982 97 713–716. (https://doi.org/10.7326/0003-4819-97-5-713)

    • Search Google Scholar
    • Export Citation
  • 5

    Marongiu F, Conti M, Mameli G, Murtas ML, Balzano S, Sorano G, Mamusa AM & Martino E Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment. Journal of Endocrinological Investigation 1988 11 72372 5. (https://doi.org/10.1007/BF03350928)

    • Search Google Scholar
    • Export Citation
  • 6

    Stuijver DJF, van Zaane B, Romualdi E, Brandjes DPM, Gerdes VEA & Squizzato A The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis. Thrombosis and Haemostasis 2012 108 107710 88. (https://doi.org/10.1160/TH12-07-0496)

    • Search Google Scholar
    • Export Citation
  • 7

    Homoncik M, Gessl A, Ferlitsch A, Jilma B & Vierhapper H Altered platelet plug formation in hyperthyroidism and hypothyroidism. Journal of Clinical Endocrinology and Metabolism 2007 92 300630 12. (https://doi.org/10.1210/jc.2006-2644)

    • Search Google Scholar
    • Export Citation
  • 8

    Tripodi A, Chantarangkul V, Martinelli I, Bucciarelli P & Mannucci PM A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism. Blood 2004 104 3631363 4. (https://doi.org/10.1182/blood-2004-03-1042)

    • Search Google Scholar
    • Export Citation
  • 9

    Erem C Thyroid disorders and hypercoagulability. Seminars in Thrombosis and Hemostasis 2011 37 1726. (https://doi.org/10.1055/s-0030-1270067)

    • Search Google Scholar
    • Export Citation
  • 10

    Kootte RS, Stuijver DJF, Dekkers OM, van Zaane B, Fliers E, Cannegieter SC & Gerdes VE The incidence of venous thromboembolism in patients with overt hyperthyroidism: a retrospective multicentre cohort study. Thrombosis and Haemostasis 2012 107 4174 22. (https://doi.org/10.1160/TH11-10-0691)

    • Search Google Scholar
    • Export Citation
  • 11

    Lin HC, Yang LY & Kang JH Increased risk of pulmonary embolism among patients with hyperthyroidism: a 5-year follow-up study. Journal of Thrombosis and Haemostasis 2010 8 217621 81. (https://doi.org/10.1111/j.1538-7836.2010.03993.x)

    • Search Google Scholar
    • Export Citation
  • 12

    Franchini M, Lippi G & Targher G Hyperthyroidism and venous thrombosis: a casual or causal association? A systematic literature review. Clinical and Applied Thrombosis/Hemostasis 2011 17 3873 92. (https://doi.org/10.1177/1076029610364521)

    • Search Google Scholar
    • Export Citation
  • 13

    ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. (available at: https://www.ahajournals.org/doi/full/10.1161/circ.104.17.2118)

    • Search Google Scholar
    • Export Citation
  • 14

    Sheu JJ, Kang JH, Lin HC & Lin HC Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up study. Stroke 2010 41 96196 6. (https://doi.org/10.1161/STROKEAHA.109.577742)

    • Search Google Scholar
    • Export Citation
  • 15

    Presti CF & Hart RG Thyrotoxicosis, atrial fibrillation, and embolism, revisited. American Heart Journal 1989 117 97697 7. (https://doi.org/10.1016/0002-8703(8990642-x)

    • Search Google Scholar
    • Export Citation
  • 16

    van Zaane B, Squizzato A, Huijgen R, van Zanten AP, Fliers E, Cannegieter SC, Büller HR, Gerdes VE & Brandjes DP Increasing levels of free thyroxine as a risk factor for a first venous thrombosis: a case-control study. Blood 2010 115 4344434 9. (https://doi.org/10.1182/blood-2009-11-253724)

    • Search Google Scholar
    • Export Citation

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  • View in gallery

    Plain CT AP showing significant gastric distension (red arrow) and fat stranding around jejunum (white arrows).

  • View in gallery

    Contrasted CT scan images showing a filling defect in left pulmonary artery (left) and extensive portal vein thrombosis (right).

  • 1

    Hirsh J, Anand SS, Halperin JL, Fuster VAmerican Heart Association. Guide to anticoagulant therapy: heparin: a statement for healthcare professionals from the American Heart Association. Circulation 2001 103 29943018. (https://doi.org/10.1161/01.cir.103.24.2994)

    • Search Google Scholar
    • Export Citation
  • 2

    Lee LH, Liu TC, Kuperan P, Tan LK, Tan D, Poon ML, Ong KH, Fong SZ, Tan MY & Ng HJ Hereditary thrombophilia in an unselected cohort of venous thrombosis patients in Singapore. Journal of Clinical Pathology 2011 64 814817. (https://doi.org/10.1136/jclinpath-2011-200018)

    • Search Google Scholar
    • Export Citation
  • 3

    Franchini M Hemostatic changes in thyroid diseases: haemostasis and thrombosis. Hematology 2006 11 20320 8. (https://doi.org/10.1080/10245330600667591)

    • Search Google Scholar
    • Export Citation
  • 4

    Rogers JS, Shane SR & Jencks FS Factor VIII activity and thyroid function. Annals of Internal Medicine 1982 97 713–716. (https://doi.org/10.7326/0003-4819-97-5-713)

    • Search Google Scholar
    • Export Citation
  • 5

    Marongiu F, Conti M, Mameli G, Murtas ML, Balzano S, Sorano G, Mamusa AM & Martino E Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment. Journal of Endocrinological Investigation 1988 11 72372 5. (https://doi.org/10.1007/BF03350928)

    • Search Google Scholar
    • Export Citation
  • 6

    Stuijver DJF, van Zaane B, Romualdi E, Brandjes DPM, Gerdes VEA & Squizzato A The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis. Thrombosis and Haemostasis 2012 108 107710 88. (https://doi.org/10.1160/TH12-07-0496)

    • Search Google Scholar
    • Export Citation
  • 7

    Homoncik M, Gessl A, Ferlitsch A, Jilma B & Vierhapper H Altered platelet plug formation in hyperthyroidism and hypothyroidism. Journal of Clinical Endocrinology and Metabolism 2007 92 300630 12. (https://doi.org/10.1210/jc.2006-2644)

    • Search Google Scholar
    • Export Citation
  • 8

    Tripodi A, Chantarangkul V, Martinelli I, Bucciarelli P & Mannucci PM A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism. Blood 2004 104 3631363 4. (https://doi.org/10.1182/blood-2004-03-1042)

    • Search Google Scholar
    • Export Citation
  • 9

    Erem C Thyroid disorders and hypercoagulability. Seminars in Thrombosis and Hemostasis 2011 37 1726. (https://doi.org/10.1055/s-0030-1270067)

    • Search Google Scholar
    • Export Citation
  • 10

    Kootte RS, Stuijver DJF, Dekkers OM, van Zaane B, Fliers E, Cannegieter SC & Gerdes VE The incidence of venous thromboembolism in patients with overt hyperthyroidism: a retrospective multicentre cohort study. Thrombosis and Haemostasis 2012 107 4174 22. (https://doi.org/10.1160/TH11-10-0691)

    • Search Google Scholar
    • Export Citation
  • 11

    Lin HC, Yang LY & Kang JH Increased risk of pulmonary embolism among patients with hyperthyroidism: a 5-year follow-up study. Journal of Thrombosis and Haemostasis 2010 8 217621 81. (https://doi.org/10.1111/j.1538-7836.2010.03993.x)

    • Search Google Scholar
    • Export Citation
  • 12

    Franchini M, Lippi G & Targher G Hyperthyroidism and venous thrombosis: a casual or causal association? A systematic literature review. Clinical and Applied Thrombosis/Hemostasis 2011 17 3873 92. (https://doi.org/10.1177/1076029610364521)

    • Search Google Scholar
    • Export Citation
  • 13

    ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. (available at: https://www.ahajournals.org/doi/full/10.1161/circ.104.17.2118)

    • Search Google Scholar
    • Export Citation
  • 14

    Sheu JJ, Kang JH, Lin HC & Lin HC Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up study. Stroke 2010 41 96196 6. (https://doi.org/10.1161/STROKEAHA.109.577742)

    • Search Google Scholar
    • Export Citation
  • 15

    Presti CF & Hart RG Thyrotoxicosis, atrial fibrillation, and embolism, revisited. American Heart Journal 1989 117 97697 7. (https://doi.org/10.1016/0002-8703(8990642-x)

    • Search Google Scholar
    • Export Citation
  • 16

    van Zaane B, Squizzato A, Huijgen R, van Zanten AP, Fliers E, Cannegieter SC, Büller HR, Gerdes VE & Brandjes DP Increasing levels of free thyroxine as a risk factor for a first venous thrombosis: a case-control study. Blood 2010 115 4344434 9. (https://doi.org/10.1182/blood-2009-11-253724)

    • Search Google Scholar
    • Export Citation