Hemolitik anemi ve immün trombositopeni nedeni ile splenektomi yapılan hastalarda pulmoner hipertansiyonun sıklığı ve risk faktörleri
The frequency and risk factors of pulmonary hypertension in patients WHO underwent splenectomy due to haemolytic anaemia and immune thrombocytopenia
Yazar: ZELİHA BİRSİN
Danışman: DOÇ. DR. AYŞE SALİHOĞLU
İstanbul Üniversitesi-Cerrahpaşa / Cerrahpaşa Tıp Fakültesi / İç Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2021
Konu: Hematoloji = Hematology ; Kardiyoloji = Cardiology
Dizin: Anemi = Anemia ; Anemi-hemolitik = Anemia-hemolytic ; Hemoliz = Hemolysis ; Hipertansiyon = Hypertension ; Hipertansiyon-pulmoner = Hypertension-pulmonary ; Risk faktörleri = Risk factors ; Splenektomi = Splenectomy ; Trombositopeni = Thrombocytopenia

Özet:
Amaç : Splenektomi sonrası PH gelişimi bildirilmiştir. Bu çalışmada, hemolitik anemilere ve İTP' ye bağlı splenektomi yapılmış olan hastalardaki PH sıklığını ve ilişkili risk faktörlerini belirlemeyi amaçladık.
Gereç ve Yöntem: İstanbul Üniversitesi-Cerrahpaşa, Cerrahpaşa Tıp Fakültesi, hematoloji bilim dalında Ocak 2000 yılından itibaren takip edilen ve bu tarihten önce ve ya sonra Temmuz 2018'e kadar splenektomi yapılmış 21 İTP ve 22 hemolitik anemili hasta çalışmaya dahil edildi. Bu hastaların EKO ile PH riskleri belirlendi, 6DYT yapıldı ve kan tetkikleri ile beraber 2015 ESC/ERS PH Tanı ve Tedavi Kılavuzundaki önerilere göre PH açısından değerlendirildi. 
Bulgular: Hastalar splenektomi sonrası EKO ile PH açısından değerlendirildiğinde; hastaların %88,3'ünde (n:38 ) EKO ile PH riski düşük iken, %11,7'sinde (n:5) orta-yüksek riskli olarak saptandı. Orta-yüksek riskli hastaların (n:5; 3 TM, 1 Tİ, 1 İTP),  %80'i (n:4) hemolitik anemi ve %20'si (n:1) ise İTP tanısı ile izlenmekteydi. İTP grubunda hiçbir hastaya PH tanısı konulmazken, hemolitik anemi grubunda beta talasemili 3 hastaya SKK ile grup 4-5 PH tanısı konulmuştur. Splenektomi sonrası hemolitik anemi ve İTP tanılı hastalar arasında EKO ile PH riski ve SKK ile PH tanısının konulması bakımından gruplar arasında istatistiksel olarak anlamlı farklılık bulunmamıştır (p>0,05). 
Sonuç : Hasta sayısındaki yetersizlikler nedeniyle, hemolitik anemi ve İTP tanılı hastalar arasında PH gelişimi açısından istatistiksel olarak anlamlı farklılık gösterilememiştir. Fakat splenektomi sonrası PH gelişimi, dalak yokluğunun bağımsız bir etkisinden ziyade altta yatan splenektomi nedeni ile ilişkili görünmektedir. Özellikle hemolitik hastalıklara bağlı splenektomi yapılan hastalarda; splenektomi sonrası hemoliz varlığı ve transfüzyon gereksinimi devam ediyor ise, PH açısından yüksek riskli oldukları düşünüldü.

Abstract:
Purpose: Splenectomy is frequently used in the treatment of haemolytic anaemia and ITP. Many infectious and vascular complications can be incident after splenectomy in the long and short term. Especially in recent years, the development of PH after splenectomy has become prominent as a vascular complication. This study aims to determine the frequency of PH and associated risk factors in patients who underwent splenectomy due to haemolytic anaemia and ITP.
Material and Method: The files of 61 patients diagnosed with haemolytic anaemia and 65 patients diagnosed with ITP, who  have been followed-up since January 2000 and who underwent splenectomy before that date or by July 2018 at Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Haemetology, were reviewed. Of these patients, 21 ITP patients and 22 haemolytic anaemia patients who underwent ECHO test in order to evaluate the development of PH after splenectomy or during routine examination due to medical necessity between the years 2019-2020, were included in the study. The demographic characteristics and post-splenectomy conditions of these patients were examined, their symptoms were enquired, PH risks were determined by ECHO, 6MWT were performed during outpatient clinic follow-ups and evaluated with routine blood tests in terms of PH. 10 patients, who were symptomatic during examinations performed due to medical necessity, who were found to have medium or high risk in terms of PH during ECHO evaluation, whose NT- pro BNP value was high and who had difficulty in 6MWT test, were examined further in terms of PH in accordance with PH diagnosis algorithms in 2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension, since they were in the group who had PAH or CTEPH risk. 
Results: The median follow-up period of patients with haemolytic anaemia and ITP after splenectomy was found to be 25 (15-43) and 9 (2-29) years, respectively. Atherosclerotic cardiovascular events were not observed in any of the patients after splenectomy. While a history of arterial (n:2, SCA) and venous thrombosis (n:2, TM) after splenectomy was observed in patients with haemolytic anaemia, no such complication developed in patients with ITP. When the patients were evaluated in terms of PH by ECHO after splenectomy; while the PH risk evaluated by ECHO was low in 88.3% of the patients (n: 38), it was found to be medium-high risk in 11.7% (n:5). Of the medium-high risk patients (n:5; 3 TM, 1 TI, 1 ITP), 80% (n:4) were being followed up with a diagnosis of haemolytic anaemia and 20% (n:1) with ITP. Amongst the patients with a diagnosis of ITP, only 1 patient had medium risk, and the remaining patients had low risk. No statistically significant difference was found between patients diagnosed with haemolytic anaemia and ITP in terms of post-splenectomy PH as evaluated by ECHO (p>0,05). Whereas no patients in the ITP group were diagnosed with PH, 3 patients with beta thalassaemia in haemolytic anaemia group were diagnosed with 4-5 PH by RHC. There was no statistically significant difference between the patients with haemolytic anaemia and ITP after splenectomy in terms of the diagnosis of RHC and PH between the groups (p>0,05). PH risk was determined to be low in patients, whose haemolysis decreased and need for transfusion disappeared after splenectomy such as HS, PKD, AIHA in patients with haemolytic anaemia. Despite the ongoing presence of haemolysis and the need for intermittent transfusion, the PH risks of patients with SCA in our study were found to be low by ECHO. In general, the diagnoses of the patients did not make a statistically significant difference between PH risks by ECHO; it led to a significant difference between laboratory parameters such as WBC, Hgb, D-dimer, NT- proBNP and ferrıtıne and 6MWT between groups (p<0,05). There was a statistically significant difference in the duration after splenectomy of patients with moderate to high ECHO risk and patients with low risk; patients with PH had a longer duration after splenectomy. In terms of PH development, patients with venous thrombosis after splenectomy were found to be at higher risk than other patients without a history of venous thrombosis (p<0,05). Patients with symptoms had a statistically significant higher TRV level than patients without symptoms (p:0,001). Contrary to expectations, haemolysis parameters (LDH, Haptoglobin, presence of erythroblast in peripheral blood smear) and the presence of thrombocytosis were not significant between patients with moderate to high ECHO risk and patients with low risk (p>0,05). 
Conclusion: Due to the insufficient number of patients, no statistically significant difference was found between patients with haemolytic anaemia and ITP in terms of the development of PH. However, the development of PH after splenectomy appears to be related to the underlying splenectomy rather than an independent effect of the absence of spleen. Especially in patients who underwent splenectomy due to haemolytic diseases; if the presence of haemolysis and the need for transfusion persisted after splenectomy, they were at higher risk for PH and other vascular complications. It was suggestive that the risk of PH was lower in patients who had splenectomy due to reasons other than haemolytic disease or who had splenectomy due to haemolytic diseases, but after splenectomy haemolysis decreased and the need for transfusion disappeared. It was concluded that in clinical practice in this patient group, it should be examined in terms of PH only if symptoms are present.