Pistolrån åhus
Pistolrån på ungdomshotellet: Parkleken Stråket: Greven som byggde slottet: Spökerier i Hässelby: Poliser utrymde matsalen: Den blinde excellensen: Den provisoriska kyrksalen: Hässelby Nöjespark: Historien om Kalvudden: Carl. When unrecognized or inappropriately treated, aHUS has a high degree of morbidity and mortality. Two-thirds of aHUS cases are associated with an identifiable complement-activating condition.
The signs and symptoms of all the TMAs overlap, complicating the differential diagnosis. Clinical identification of a TMA requires documentation of microangiopathic hemolysis accompanied by thrombocytopenia. DIC must be recognized and treated before it is possible to discriminate among the other 3 major TMAs. This test, as both an activity assay and an inhibitor assay, should be ordered before the initiation of plasma therapy in any patient presenting with a TMA.
Finally, it is important to recognize that aHUS remains a clinical diagnosis, but in complex scenarios, tissue biopsy may be a useful adjunct in diagnosis. Clinical recognition of any TMA requires the documentation of microangiopathic hemolysis—with fragmented red blood cells or schistocytes on peripheral blood smear, low haptoglobin levels, elevated lactate dehydrogenase LDH and indirect bilirubin, and a decline in baseline hemoglobin—accompanied by throm-bocytopenia.
These laboratory changes must occur in concert with clinical involvement of at least 1 organ system, the most common sites being the central nervous system, the kidneys, and the gastrointestinal tract. DIC, usually secondary to infection or malignancy, stands apart from the other TMAs because it has characteristic laboratory abnormalities indicative of a consumptive coagulopathy, including an elevated international normalized ratio INR and activated partial thromboplastin time aPTT.
However, the signs and symptoms of all the TMAs overlap extensively, complicating the differential diagnosis. Since the initial descriptions of 2 major categories of TMA—TTP by Moschcowitz in 6 and HUS by Gasser in 7 —there have been but a handful of critical diagnostic and therapeutic breakthroughs. This was followed by isolation of Shiga toxin—producing E. The high morbidity and mortality associated with untreated TTP and aHUS, and the different managements they require, mandate timely recognition of a TMA, followed by the ability to distinguish between the 2 conditions.
This review highlights the differences in pathophysiology and diagnostic findings among the TMAs, expanding the original article with new references to genetic data and tissue biopsy. This information should permit a well-structured diagnostic approach to patients presenting with a TMA, facilitating institution of appropriate therapeutics.
Atypical Hemolytic Uremic Syndrome
Development of TTP and aHUS appears to require 2 conditions: 1 pre-existing susceptibility factors that are either familial ie, genetic or acquired, and are capable of promoting endothelial cell activation, platelet aggregation, or both; and 2 modulating factors, encompassing a variety of infectious, inflammatory, autoimmune, stress, or drug-related conditions, that are linked epi-demiologically to both TTP and aHUS, and that can injure the endothelium and, often, activate complement.
The latter would account, at least in part, for the sporadic development of overt clinical signs and symptoms of disorders predicated on congenital susceptibilities.
For example, the first clinical manifestation of familial TTP, or Upshaw-Schulman syndrome, re—lated to loss-of-function gene mutations in ADAMTS13, may not occur until late in adolescence, and relapses are infrequent. This leads to propagation of platelet aggregates, related to the inability to cleave long tethers of platelets bound to ultra—high-molecular-weight multi-mers of vWF, which requires an intact ADAMTS The resultant systemic, uncontrolled microthrombus formation is clinically devastating.
As discussed below, they are genetic defects in complement and complement regulatory proteins that permit unregulated amplification of the alternative complement pathway. The consequences are massive terminal complement pathway activation with generation of C5a a potent anaphylatoxin and C5b-9 known as membrane attack complex [MAC] , triggering inflammation, platelet activation, platelet aggregation, erythrocyte lysis, endothelial cell injury, and fibrin microthrombus formation throughout the microvasculature.
In approximately two-thirds of aHUS cases, the TMA is manifested by a recognized complement-activating condition, which causes endothelial cell damage in concert with complement activation, in a person with the congenital inability to control complement. These conditions are listed in Table 2.
Atypical Hemolytic Uremic Syndrome (aHUS): Essential Aspects of an Accurate Diagnosis
They include infections with a wide variety of microorganisms prominent ones are H1N1 influenza and those in the vaccines for H1N1, adenovirus, cytomegalovirus, Streptococcus pneumoniae , and STEC , pregnancy, malignant hypertension, surgery, organ and tissue transplant, and malignancy. As reviewed in Section III. One must first treat that initial disease process adequately. If the TMA does not resolve, then consider that it unmasked aHUS, which should then be viewed as the primary cause of patient morbidity and therefore treated.
Making this distinction may require special diagnostic tools, including tissue biopsy, as discussed in section VI. Given the pathophysiologic differences between aHUS and TTP, one might think that diagnostic criteria to distinguish among the TMAs would be relatively simple to apply. Often they are, and this is critical clinically, as it will guide management decisions. Recognize a TMA. As outlined in Table 1 and Figure 1, clinical recognition of a TMA involves documentation of the principle laboratory criteria for microangiopathic hemolytic anemia—schistocytes on peripheral blood smear, elevated LDH, low haptoglobin, elevated indirect bilirubin, and a decline in baseline hemoglobin—accompanied by thrombocytopenia.
Not all of these changes are necessary to make a TMA diagnosis. The rationale for this statement is discussed below. All TMAs may be associated with thrombocytopenia, red cell fragmentation, and release of D-dimers and fibrin degradation products. If DIC is present, the underlying condition must first be corrected. Although indirect bilirubin is often within the normal range in DIC, the bilirubin may not be elevated, at least initially, in other TMAs as well, even in the context of a markedly elevated LDH see below.
However, they may be infrequent on initial presentation, overlapping with levels in healthy controls of 1 or less per high-power microscopic field. Intact reticuloendothelial and splenic function is capable of clearing red cells with damaged membranes—eg, schistocytes—from the periphery for several days, despite other laboratory and clinical manifestations of a TMA. This argues for daily review of the peripheral blood smear to evaluate changes in schistocyte frequency.
Biopsy may be useful in the absence of peripheral schistocytes, as characteristic features of a TMA in tissue can still be present, as discussed in section VI.