NDT Advance Access published online on April 14, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn177
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reply
Correspondence and offprint requests to: E-mail: stefan.herget-rosenthal{at}uni-due.deSir,
Dr Thachil correctly highlights the important association of thrombotic thrombocytopenic purpura (TTP) and acute myocardial infarction (AMI) which is consistent with our and others’ findings [1,2]. The clinical relevance of this severe TTP complication is further emphasized by recent case series and case reports that describe 12 additional cases of AMI associated with TTP [3]. Furthermore, the author presents two interesting pathophysiological hypothesis which may link TTP with AMI. First, increased levels of ultralarge multimers of the von Willebrand factor (vWF) as present in TTP by decreased or inhibited ADAMTS13, the vWF cleaving enzyme, were associated with adverse outcome in AMI. Secondly, free haemoglobin released by haemolysis during TTP captures nitric oxide (NO). Decreased levels of NO in turn could reduce inhibition of platelet aggregation and coronary vasoconstriction, which are potential factors to induce or aggravate AMI.
However, we would like to comment on several aspects of this letter that put some of the statements provided into perspective. Although AMI has predominately been described in TTP, it is also associated with other types of thrombotic microangiopathy (TMA). These TMA types which account for the majority of all cases, frequently differ from TTP in respect to their pathophysiology, lack of association with decreased or inhibited ADAMTS13 and response to plasma exchange [4]. Despite the effects of NO on coronary vasomotor tone and platelet activation, both effects are moderate, and other major control pathways require consideration in this context. While endothelin and 
-adrenoceptors agonists mediate coronary vasoconstriction, adenosine, ATP-dependent K+-channels, endothelium-derived hyperpolarizing factor and β-adrenoceptors agonists cause coronary vasodilatation [5]. Likewise, there are several factors such as adenosine diphosphate, thromboxane A2, thrombin, epinephrine, collagen and platelet activating factor which provoke platelet activation and adhesion and prostacycline as a second major inhibitor of platelet adhesion [6]. Additionally, the reduction of NO by itself does not induce spontaneous platelet aggregation but requires prior platelet activation by cofactors as a prerequisite. Thus, the effect of absent NO remains speculative, provides only limited explanation and these other pathways described need to be taken into account. Finally, TTP and TMA are characterized by severe injury and activation of the vascular endothelium that in all likelihood will result in the release of most of these factors favouring microvascular coronary thrombosis [4].
The intriguing idea to administer NO donors as nitrates to patients with TTP certainly deserves to be studied. As no data exist on the effect of NO donation in TTP, detailed studies are required. However, we caution against applying nitrates at present outside of any trial, as TTP may induce sudden haemodynamic shock and multiorgan failure, life-threatening situations which may be aggravated by the use of nitrates.
Conflict of interest statement. None declared.
Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
References
- Patschan D, Witzke O, Dührsen U, et al. Acute myocardial infarction in thrombotic microangiopathies—clinical characteristics, risk factors and outcome. Nephrol Dial Transplant (2006) 21:1549–1554.
[Abstract/Free Full Text] - Hawkins BM, Abu-Fadel M, Vesely SK, et al. Clinical cardiac involvement in thrombotic thrombocytopenic purpura: a systematic review. Transfusion (2008) 48:382–392.[Web of Science][Medline]
- Perez L, Ramappa P, Guzman JA. Myocardial injury in thrombotic thrombocytopenic purpura: a frequent, perplexing complication. Int J Cardiol (2007) in press.
- Herget-Rosenthal S. Thrombotic microangiopathies—an issue for intensivists? Acta Clin Belg (2007) 62(Suppl. 2):385–388.[Web of Science]
- Tune JD, Gorman MW, Feigl EO. Matching coronary blood flow to myocardial oxygen consumption. J Appl Physiol (2004) 97:404–415.
[Abstract/Free Full Text] - Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med (2007) 357:2482–2494.
[Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||