[Chronic disseminated intravascular coagulation (DIC) markers in a patient with multiple angiomatosis during treatment with anti-angiogenics: interferon α, thalidomide and lenalidomide]. / Vývoj koagulacních markeru chronické diseminované intravaskulární koagulace (DIK) u pacienta s mnohocetnou angiomatózou v prubehu lécby antiangiogenními léky: interferonem α, thalidomidem a lenalidomidem.

BACKGROUND: Multiple angiomatosis is a rare disease with angiomatous formations in multiple organs and tissues and associated with a risk of fatal bleeding. CASE DESCRIPTION: In this patient, the bones, pleural and peritoneal cavities and digestive tract were involved. The patient had long-term been administered zoledronate that provided relief from bone pain as early as after the second dose. The effect of antiangiogenics was evaluated on CT and MRI. Since angiomatous proliferation is associated with chronic disseminated intravascular coagulation (DIC) and anaemisation, blood count and fibrinogen as well as D-dimer and soluble fibrin monomer concentrations are also used to assess treatment response. RESULTS: Before treatment, D-dimer levels were in excess of 20 µg/mL, fibrinogen 1.4 g/L and soluble fibrin monomers were at measurable levels. During treatment with interferon α at a dose of 6 million units 3 times a week with the dose reduction after 10 month, the median fibrinogen concentration increased to 1.5 (1.2-2.0) g/L, the median D-dimer levels declined to 17.2 (13.4-20.0) µg/mL and fibrin monomers were still detectable. Thalidomide therapy (100 mg/day) provided reduction in the median D-dimer levels to 6.07 (4.71-10.21) µg/ml and increase in median fibrinogen concentration to 1.9 g/L; soluble fibrin monomers were unidentifiable. CT imaging suggested significant reduction of angiomatous mass. Progressing neuropathy required dose reduction of thalidomide to 50 mg/day, leading to D-dimer increase. Lenalidomide 10 mg/day provided an increase in median D-dimer concentration to 10.8 (10.8-17.35) and decline in the level of haemoglobin to a median of 124 (135-117) g/L. Soluble fibrin monomers became detectable again. Therefore, a low dose of lenalidomide 10 mg/day was combined with thalidomide 100 mg and, subsequently, 50 mg/day. Treatment with lenalidomide 10 mg and thalidomide 50 mg provided median D-dimer levels of 9.32 and the disease has remained stable for 9 months. CONCLUSION: Thalidomide 100 mg/day stabilized multiple angiomatosis better than interferon alfa. Thalidomide 50 mg/day was insufficient to maintain disease stability. Lenalidomide at a dose of 10 mg was tolerated really well but this dose was insufficient to maintain low D-dimer levels and normal haemoglobin concentrations. The combination of lenalidomide 10 mg and thalidomide 50 mg daily stabilized the disease for 9 months.

[Six-year follow-up of a patient with multiple angiomatosis involving skeleton, thoracic and abdominal cavities and the gut wall]. / Sestileté sledování pacienta s mnohocetnou angiomatózou postihující skelet, brisní i hrudní dutinu a stenu trávicí trubice.

BACKGROUNDS: Multiple angiomatosis is a rare disease causing angiomatous lesions in multiple organs and tissues with a risk of life-threatening haemorrhage. OBSERVATION: A young man was diagnosed with multiple angiomatosis at the age of 28 after two years of back and abdominal pain. Laparotomy revealed multiple spongy lesions mostly within the retroperitoneal space. Also, an involvement of the gut wall, bones and mediastinum was evident. After 6 years of treatment, the disease has been stabilized. Bone pain ceased with a significant contribution of zoledronate. Using CT and MR imaging, the effectiveness of antiangiogenic drugs was evaluated. Furthermore, treatment response was evaluated using laboratory values for coagulation and blood count, as angiomatous proliferation is known to be associated with disseminated intravascular coagulation and anaemia. RESULTS: Baseline laboratory examination revealed elevated D-dimer (more than 20 µg/mL), low fibrinogen (1.4 g/L), and the presence of fibrin monomers. After treatment with 6 mil. IU of interferon-alpha thrice weekly, there was only partial improvement in D-dimer (17.2 µg/mL) and fibrinogen (1.5 g/L) concentrations but fibrin monomers remained positive. After thalidomide (100 mg daily), D-dimer decreased to 6.1 µg/mL and fibrinogen levels increased to 1.9 g/L with the disappearance of fibrin monomers. CT scanning showed significant regression of angiomatous lesions. Progressive neuropathy was the reason to lower the dose of thalidomide by half and this caused D-dimer to rise again. Switching to lenalidomide 10 mg daily led to an increase in D-dimer to 10.8 µg/mL and decrease in haemoglobin concentration to 124 g/L. Fibrin monomers became positive again. Combined therapy with thalidomide (50 mg/day) and lenalidomide (10 mg days 1-21 in 28-day cycles) has led to stabilisation of the disease. Median concentration of haemoglobin increased to 131 (84-141) g/l. The median of D-dimer decreased to 9.3 (8.0-17) µg/mL. CONCLUSION: Thalidomide in the dose of 100 mg daily led to better stabilisation of the disease than interferon-alpha. However, lowering the dose because of adverse effects failed to be effective sufficiently. Lenalidomide 10 mg daily was well-tolerated but insufficient to improve D-dimer and haemoglobin concentrations. Therefore, for further treatment we have decided to use the combination of lenalidomide and thalidomide in doses of 10 mg and 50 mg, respectively because both drugs have desirable antiangiogenic activities with different adverse effect profiles. On this therapy, the patients disease has been stable for 9 months.

[Treatment of multiple angiomatosis involving the skeleton and the abdominal and thoracic cavities with interferon alpha, thalidomide and zoledronate]. / Lécba mnohocetné angiomatózy postihující skelet, brisní i hrudní dutinu interferonem alpha, thalidomidem a zoledronátem.

Multiple angiomatosis is a very rare disease formed by histologically benign angiomas spreading beyond single organ or tissue. In the case reported herein, hemangiomas affected several vertebrae of a young man and spread through his peritoneal cavity projecting to his stomach and causing recurrent hematemesis. Also affected was the mediastinum. The patient suffered from bone pain and digestive problems. Initial treatment involved 2 drugs with antiangiogenic effect: interferon alpha (initial dose of6 million units 3 times a week, later reduced to 3 million units 3 times a week due to adverse effects) and zoledronate (4 mg i.v. every 28 days). Even though the therapy eliminated bone pain after 2 months, CT check at a later stage showed but little regression of the mass of the angiomas in the abdominal cavity and the mediastinum. Substantial reduction in the mass of the angiomas to merely residual quantity, i.e. partial remission of the disease, was achieved only after the addition of 100 mg/day thalidomide (Myrin) to the above mentioned doses of interferon and zoledronate administered on a regular basis. However, the disease recurred after the therapy was interrupted, and the above triple combination therapy has had to be restored. Maintenance therapy will succeed to repeated achievement of remission of angiomas. A very good therapeutic effect was recorded for combined interferon alpha, thalidomide and zoledronate in this specific case of multiple angiomatosis.