Long-term follow-up studies have consistently demonstrated that incomplete perfusion recovery, even years after acute pulmonary embolism, occurs in approximately one-third of patients. Chronic thromboembolic pulmonary hypertension (CTEPH) represents the most severe end of the spectrum of failed clot resolution since right heart failure and death are the ultimate consequences of CTEPH if patients are not treated. Even so, the progression of unresolved pulmonary thrombi to CTEPH with progressive pulmonary arteriopathy remains poorly understood.
The main subject of this Virchow program will be to further unravel the transition from acute to chronic pulmonary embolism, both via clinical and translational research projects. We aim to construct an accurate and clinically applicable risk model for predicting the occurrence of CTEPH, as well as to validate a dedicated screening program for this severe complication in the natural course of acute pulmonary embolism. In addition, we will improve our understanding of the pathophysiological mechanisms behind unresolved thrombi and the resulting increase in pulmonary artery resistance by linking risk factors for CTEPH to relevant biomarkers, and verifying observed clinical correlations in animal models of thrombosis.
Mentor of the Virchow-Fellow is Professor Stavros Konstantinides, MD Head of the Module Clinical Trials at the CTH.
08/1994 - 06/2000
Gymnasium, Reynaert College, Hulst, the Netherlands
09/2000 - 09/2004
Master's degree in Medicine, Leiden University, Leiden, the Netherlands
09/2004 - 12/2006
MD degree, Leiden University, Leiden, the Netherlands
01/2007 - 12/2009
PhD fellow, Leiden University, Leiden, the Netherlands
Cum laude PhD degree, thesis entitled “Pulmonary embolism, diagnostic management and prognosis”
01/2010 - 04/2012
Clinical resident in training to be internist, Bronovo Hospital, the Hague, the Netherlands
05/2012 - now
Clinical resident in training to be internist, Leiden University Medical Hospital, Leiden, the Netherlands
11/2013 - now
Post-doctoral research fellow within the Virchow-Fellowship-Program, Centrum für Thrombose und Hämostase, Universitätsmedizin Mainz
- Klok FA, Niemann C, Dellas C, Hasenfuss G, Konstantinides S, Lankeit M. Performance of five different bleeding-prediction scores in patients with acute pulmonary embolism. Journal of thrombosis and thrombolysis 41:312-320. 2016.
- Klok FA, Dzikowska-Diduch O, Kostrubiec M, Vliegen HW, Pruszczyk P, Hasenfuss G, Huisman MV, Konstantinides S, Lankeit M. Derivation of a clinical prediction score for chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Journal of thrombosis and haemostasis 14:121-128. 2016.
- Klok FA, Tesche C, Rappold L, Dellas C, Hasenfuss G, Huisman MV, Konstantinides S, Lankeit M. External validation of a simple non-invasive algorithm to rule out chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Thrombosis research 135:796-801, 2015.
- Klok FA, Kooiman J, Huisman MV, Konstantinides S, Lankeit M. Predicting anticoagulant-related bleeding in patients with venous thromboembolism: a clinically oriented review. The European respiratory journal 45:201-210, 2015.
- Klok FA, van der Hulle T, den Exter PL, Lankeit M, Huisman MV, Konstantinides S. The post-PE syndrome: a new concept for chronic complications of pulmonary embolism. Blood reviews 28:221-226, 2014.
- den Exter PL, van der Hulle T, Lankeit M, Huisman MV, Klok FA. Long-term clinical course of acute pulmonary embolism. Blood reviews 27:185-192, 2013.
- van der Hulle T, Tan M, den Exter PL, Mol GC, del Sol AI, van de Ree MA, Huisman MV, Klok FA. Selective D-dimer testing strategy for the diagnosis of acute deep vein thrombosis – a validation study. J Thromb Haemost 2013; in press
- den Exter PL, van Es J, Klok FA, Kroft LJM, Kruip MJH, Kamphuizen PW, Buller HR, Huisman MV. Risk profile and short-term outcome of symptomatic isolated subsegmental pulmonary embolism. Blood 2013; 122:1144-9
- den Exter PL, van Es J, Erkens PMG, van Roosmalen MJG, van den Hoven P, Hovens M, Kamphuisen PW, Klok FA, Huisman MV. Impact of delays in clinical presentation on the diagnostic management and prognosis of patients with suspected pulmonary embolism. Am J Resp Crit Care Med 2013; 187:1369-73
- Huisman MV, Klok FA. How I diagnose pulmonary embolism. Blood 2013; 121:4443-8
- Douma RA, Mos ICM, Erkens PMG, Nizet TA, Durian M, Hovens M, van Houten AA, Hofstee HMA, Klok FA, ten Cate H, Ullmann HF, Büller HR, Kamphuisen PW, Huisman MV. Safety and clinical utility of four clinical decision rules in the diagnostic management of acute pulmonary embolism - the Prometheus Diagnosis Study. Ann Int Med 2011; 154:709-18
- Klok FA, van der Bijl N, Huisman MV, van Rooden CJ, Mertens BJA, de Roos A, Kroft LJM. Usefulness of ECG-synchronized MDCT-assessed right- and left ventricular function for predicting short-term clinical outcome in patients with clinically suspected acute pulmonary embolism. Chest 2011; 140:1008-15
- Klok FA, van Kralingen KW, van Dijk APJ, Heyning FH, Vliegen HW, Kaptein AA, Huisman MV. Quality of life in long-term survivors of acute pulmonary embolism. Chest 2010; 138;1432-40
- Klok FA, van der Bijl N, Eikenboom HCJ, van Rooden CJ, de Roos A, Kroft LJM, Huisman MV. Comparison of CT assessed right ventricular size and cardiac biomarkers for predicting short term clinical outcome in normotensive patients suspected for having acute pulmonary embolism. J Thromb Haemost 2010; 8:853-6
- Klok FA, van Kralingen KW, van Dijk APJ, Heyning FH, Vliegen HW, Huisman MV. Prospective cardiopulmonary screening program to detect chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism. Haematologica 2010; 95:970-5
- Klok FA, Zondag W, van Kralingen KW, van Dijk APJ, Tamsma JT, Heyning FH, Vliegen HW, Huisman MV. Patient outcomes after acute pulmonary embolism: a pooled survival analysis of different adverse events. Am J Respir Crit Care Med 2010; 181:501-6
- Klok FA, Mos ICM, Broek L, Tamsma JT, Rosendaal FR, de Roos A, Huisman MV. Risk of arterial cardiovascular events in patients after pulmonary embolism. Blood 2009; 114:1484-8
- Klok FA, Karami Djurabi R, Velthuis SI, Nijkeuter M, Huisman MV. D-dimer testing in patients with clinically suspected pulmonary embolism and impaired renal function. Am J Med 2009; 122:1050-3
- Klok FA, Mos ICM, Huisman MV. Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism - a systematic review and meta-analysis. Am J Respir Crit Care Med 2008; 178:425-30