Italiano Farmacia on line: comprare cialis senza ricetta, acquistare viagra internet.

Annals of Clinical Psychiatry, Vol. 12, No. 1, 2000 Neuroleptic Malignant Syndrome and Severe
Thrombocytopenia: Case Report and Literature Review

Shareh O. Ghani,1,3 Waqas Ahmed,2 and Luis A. Marco1
We report an unusual case of thrombocytopenia associated with neuroleptic malignantsyndrome (NMS). A 31-year-old Black male with a history of hypertension, partial seizures,and schizophrenia developed acute rigidity closely followed by severe hyperpyrexia (tempera-ture 102ЊF), tachypnea, and tachycardia. His home medications at the time of presentationincluded propanolol 10 mg tid, haloperidol 10 mg bid, sodium valproate 500 mg bid, benztro-pine 1 mg bid, and haloperidol decanoate 100 mg i.m. every 3 weeks, from another psychiatricfacility. Despite vigorous therapy for the hyperthermia, he rapidly developed significanthypoxia requiring mechanical ventilation. A diagnosis of neuroleptic malignant syndromewas made and the patient continued to receive aggressive supportive care. On hospital day2 his platelet count dropped to 47,000/Ȑl and bottomed out at 36,000/Ȑl by day 3 with otherblood cell counts remaining within normal limits. Over the next few days he showed rapidclinical improvement with normalization of his blood chemistries and he was dischargedhome after 5 days of hospitalization in good condition.
KEY WORDS: neuroleptic malignant syndrome; thrombocytopenia; neuroleptics.
chlorperazine administration in 1963 (3). IsolatedNL-induced thrombocytopenia is a more rare occur- Blood dyscrasias occur as a frequent side effect rence, but it has been reported three times during of neuroleptic (NL) administration, the most serious being agranulocytosis and, of less concern, granulocy- However, in a study encompassing one entire topenia. NL-induced thrombocytopenia is fairly un- year of observations no clinical differences were common and usually occurs concomitantly with leu- found between NL-treated and untreated schizo- kopenia. Indeed, in a 6-year course study, the largest phrenics. Yet, there was a suggestion of a trend, as reported series in the world literature, by Rosebush three of the NL-treated patients had platelet counts and Stewart (1), elevated platelet count rather than of less than 150,000/Ȑl. It is unkown whether the thrombocytopenia was the most frequent finding.
development of neuroleptic malignant syndrome Two fatal cases of coexistent leukopenia and (NMS) increases the risk of agranulocytosis, leukope- thrombocytopenia were reported in the past; one was nia, thrombocytopenia, or a combination of these a 28-year-old female patient receiving chlorproma- blood abnormalities. But it appears that isolated zine (2) and the other secondary to jaundice, agranu- thrombocytopenia associated with NMS is also un- locytosis, and thrombocytopenia associated with pro- common. Indeed, no cases were reported throughouta time span of almost two decades, beginning in 1976 1Department of Psychiatry, University of South Alabama, Mo- (7), and only three cases during the last 3–4 years despite awareness of the NMS since it was first re- 2Department of Internal Medicine, University of South Alabama, ported in 1968 (8). It is not known whether thrombo- 3Correspondence should be addressed to Shareh O. Ghani, M.D., cytopenia was reported in conjunction with NMS be- 304 Rural Street, Evergreen, Alabama 36401.
tween 1968 and 1976, and also since the introduction 1040-1237/00/0300-0051$18.00/1  2000 American Academy of Clinical Psychiatrists Ghani, Ahmed, and Marco
of NL agents for the treatment of psychosis in France the brain, a lumbar puncture, and an EKG were done in the early 1950s. It would be informative to know and were found to be unremarkable. Laboratory data whether such cases were ever reported. This would from the local county hospital showed the following reinforce the cause–effect connection or at least the findings from blood drawn at the time the patient correlation between NMS and thrombocytopenia, was initially brought to them. A WBC count of which at this stage cannot go beyond the level of high 148,000/Ȑl, platelets at 211,000/Ȑl (with no abnor- suspicion. It is intriguing that all the four cases so far malities on peripheral smear), a serum sodium of 129 reported were patients in their early to middle 30s mEq/L, a potassium of 4.4 meq/L, a BUN of 9 mg/ including the lethal case reported by Lenler-Peterson dl, and a creatinine of 2.2 mg/dl. CPK was 973 U/L.
et al. (9). These authors had already pointed out that He was admitted to the ICU and received supportive NMS is overrepresented in young patients.
care. On hospital day 2 his platelet counts acutelydropped to 47,000/Ȑl, but with no signs of activebleeding. On day 3 his platelets further dropped to CASE REPORT
36,000/Ȑl. He had a minimal nosebleed. The next dayhis platelets increased to 46,000/Ȑl. Prothrombin time A 31-year-old black Male with a history of hy- was increased to 15.7 sec (N: 10.7–14.3) on day 1 and pertension, partial seizure disorder, and schizophre- 14.7 on day 3, which was marginally high, but the nia was admitted to a local county hospital with acute partial thromboplastin time was normal throughout onset of severe rigidity and unresponsiveness. His home medications included propranolol 10 mg three He began to wake up on day 2 and was extubated times a day, haloperidol 10 mg twice a day, valproic the same day. He remained afebrile and improved acid 500 mg twice a day, benztropine 1 mg three times rapidly over the next 2 days with his mental status a day, and haloperidol decanoate 100 mg intramuscu- reverting to baseline. His platelet count increase par- larly every 2–3 weeks. He had received the most alleled his symptomatic improvement and on the day recent injection of haloperidol decanoate 2 days prior of discharge the platelet count was 86,000/Ȑl. His to presentation. According to the patient’s family, he peak CPK levels reached 1324 U/L by day 3 and had been in his usual state of health 1 day prior to then dropped to 387 U/L by day 5 prior to discharge hospitalization when he started to develop agitation (Table 1). No evidence of renal insufficiency was with increasing body stiffness. He began to breathe at noted during his stay. A drug and alcohol screen was a rapid rate with a decreasing level of consciousness.
negative. Initially his differential diagnosis included Upon arrival at the local hospital he was found an infectious process, specifically meningitis, but the to be unresponsive and extremely rigid, with a core blood and spinal fluid cultures remained negative temperature of 108.7ЊF. His heart rate was 120 beats/ min, his blood pressure was 160/70 mm Hg, and hisrespiratory rate was 20/min. His skin was hot anddry. The remainder of the physical exam was unre- DISCUSSION
markable. A diagnosis of neuroleptic malignant syn-drome was made and the patient received one dose A hypothesis has been proposed by Yao et al. of dantrolene 2 mg/kg intravenously. He received (10) to explain the concomitance of thrombocyto- vigorous therapy for his hyperthermia with cooling penia and NMS. It is based on their findings that blankets, ice packs, and gastric lavage with iced nor- thrombin-induced platelet production of inositol mal saline. While in the emergency room he startedto become bradypneic with a falling oxygen satura-tion, was intubated, and was placed on artificial venti- Table 1. Laboratory Data
lation. Within a few hours his temperature decreased to 102.8ЊF and he was transferred to the UniversityHospital.
Upon arrival he was minimally responsive to painful stimuli. His vital signs showed a blood pres- sure of 118/74 mm Hg, a heart rate of 75/min, and a temperature of 97.2ЊF. Physical examination was positive for minimal muscular rigidity. A CT scan of Neuroleptic Malignant Syndrome and Severe Thrombocytopenia
phosphates (IP) is higher in haloperidol-treated as stimulation of their platelet membranes persists for well as untreated schizophrenics. This means that at least 2 months even after acute psychotic symptoms schizophrenics may produce higher levels of IP than nonschizophrenics and that the source of the extra- IP may reside in the platelets. On the other hand, cAMP function have been demonstrated in platelets NL-induced blockage of dopamine also contributes of schizophrenic patients. These changes in turn are to a serum increase in IP levels, which would in turn thought to cause inhibition of the IP3/Ca2ϩ pathway, potentiate activation of protein kinase C (11). These lowering IP turnover, increased activation of protein findings suggest that there may be an increased signal kinase C, and reduction in protein kinase A activity transduction in schizophrenia and that this state may and calmodulin-dependent protein kinase. Since neu- be mediated through neuroleptic-regulated IP hydro- rons respond in ways similar to platelets, it is thought that such a cascade of events may not be restricted However, understanding of the mechanisms re- to platelets, but may also involve the brain, causing sponsible for IP synthesis, breakdown, and regulation a distorted balance of protein activation via phos- in schizophrenia in NL-treated and untreated pa- phorylation in neurons and further deficits of schizo- tients is still very rudimentary. It is intriguing to con- phrenia (11) compounded with NMS. Ray (7) enter- sider that platelets are comparable to catecholamin- tained the possibility that these mechanisms might ergic neurons (12) and as such they may represent trigger a cascade of events leading to further platelet an acceptable model of a neurosecretory cell to inves- activation and aggregation, as expected under normal tigate membrane-dependent functions such as signal circumstances. Ray (7) went on to postulate that a transduction in schizophrenic disorders (10). Throm- hyperdynamic pathway may thus be opened that bin is a potent agonist leading to the activation of would lead to thrombocytopenia. Ray realized, how- phospholipases C and A2, protein kinases, IP, and ever, that this postulate fails to explain why no clinical Ca2ϩ mobilization. All of these factors are involved evidence of microvessal thrombosis has yet been ob- in platelet adhesion to endothelial membranes and aggregation with each other. Adhesion and aggrega- However, the rapidly progressing lethal case re- tion are two important processes of platelet function.
ported by Lenler-Peterson et al. (9) was complicated The result of these enzymatic reactions is generation by disseminated intravascular coagulation. No defin- of diacylglycerol (DAG) and inositol triphosphate itive answers to the questions posed above are avail- (IP3), which are the second messengers activating able at this point, but clinicians need to be aware of protein kinase C and mobilizing calcium (Ca2ϩ) from the possible cooccurrence of NMS and thrombocyto- intracellular stores. With these transduction mecha- penia. It might be possible to explain the causation nisms there is a built-in regulation of phospholipase of thrombocytopenia by other mechanisms. For ex- C (PLC)-induced hydrolysis of IP3 and ion channels.
ample, large groups of patients on tricyclic antide- These early biochemical breakdowns are responsible pressants, carbamazepine, and valproate have been for the signal transduction to move from the mem- studied for their proclivity to develop blood dyscra- brane surface receptor to the cell interior. This sias (15,16). According to Tohen et al. (16), severe formation of IP3 is significantly higher in haloperidol- blood dyscrasias, specifically leukopenia, are uncom- treated schizophrenics than in drug-naive schizo- mon in psychiatric patients treated with valproate, phrenics or normal controls (13). This increased pro- just as they are with carbamazepine, imipramine, or duction of IPs appears, therefore, to be the result of desipramine. Blood dyscrasias are also most likely to NL treatment. Furthermore, such drug effect may follow within the first 45 days of treatment. The study often endure for 4 months after NL withdrawal (13).
by Loiseau (15) is more relevant to our discussion Subsequent biochemical products of IP metabolism because here the focus was valproate as a cause of are conversion of IPs to DAG and phosphatidic acid platelet dysfunction. The conclusion of this study was (PA). It has been claimed that schizophrenics with that valproate can provoke, infrequently, a thrombo- abnormal IP turnover would have a better outcome cytopenia which does not appear to have much clini- than those without it, meaning that accumulation of cal significance except in surgical patients, obviously DAG in schizophrenia may be a marker of good because of the risk of hemorrhage. The authors rec- prognosis (14), but this would require confirmation.
ommendation was that valproate doses of 40 mg/kg/ We do know that the accumulation of DAG in the day should not be exceeded. Our patient was main- platelets of acute schizophrenics following thrombin tained at 500 mg twice daily, which is close to the Ghani, Ahmed, and Marco
maximum dose recommended by Loiseau (15), who such as thioridazine, have been reported to cause felt that the risk of hematological abnormalities is thrombocytopenia; haloperidol was also suggested as often dose-related. Vadney (17) also reported in 1992 a possible cause at least for the initial platelet decline an association between valproate administration, vi- ral infection, particularly varicella, and thrombocyto-penia, a correlation which would be clinically usefulto keep in mind.
No reason to suspect viral infection was found REFERENCES
during our patient’s laboratory work-up. For the rea- 1. Rosebush P, Stewart T: A prospective analysis of 24 episodes sons mentioned above (rarity of cooccurrence, usu- of neuroleptic malignant syndrome. Am J Psychiatry 1989; ally during the first 45 days of treatment, and our patient’s relatively low dose of valproate), we do not 2. Swett CC: Adverse reactions to chlorpromazine in medical patients: A report from the Boston Collaborative Drug Sur- feel that the probability of valproate being the cause veillance Program. Curr Ther Res 1975; 18:199–206 of our patient’s thrombocytopenia is very high, but 3. McFarland RB: Fatal drug reaction associated with pro- we have no way to rule this out with certainty.
chlorperazine (compazine). Report of a case characterized byjaundice, thrombocytopenia, and agranulocytosis. Am J Clin Even though dantrolene has been used for quite some time in the treatment of NMS, there is no evi- 4. Storrie MC, Scher M, McGuire J, Bokan J: Thrombocytopenia dence that it alters the course of this disease in any with absence of leukopenia associated with the use of neuro-leptics. J Clin Psychiatry 1978; 72:779–782 way (1). There are anecdotal case reports similar to 5. Holt RJ: Neuroleptic drug-induced changes in platelet levels: ours that may suggest a possible effect on NMS, but there is insufficient evidence to recommend dantro- 6. Balon R, Berchou R: Hematologic side effects of psychotropic drugs. Psychosomatics 1986; 217:119–127 7. Ray JG: Neuroleptic malignant syndrome associated with We were concerned with the risk of spontaneous thrombocytopenia. J Intern Med 1997; 241:245–247 bleeding in our patient, but a review of the literature 8. Delay J, Deniker P: Drug induced extrapyramidal syndromes.
In: Vinken RJ, Bruyn GW, eds. Handbook of Clinical Neurol- was reassuring, as other authors had reported no ogy: Disease of the Basal Ganglia, Vol. 6, New York, Elsevier evidence of bleeding and that bleeding may occur only after platelet counts fall below 19,000/Ȑl (4).
9. Lenler-Peterson P, Hausen BD, Hasselstorm L: A rapidly progressing lethal case of neuroleptic malignant syndrome.
This study, although it did not involve a picture of NMS, nevertheless concluded, based on a spleen scan 10. Yao JK, Yassai P, Van Kammen DP: Increased turnover of to rule out an inordinate amount of spleen sequester- platelet phosphotidyl inositol in schizophrenia, ProstaglandinsLeukotrienes Essential Fatty Acids 1992; 46:38–46 ing platelets, that platelets were breaking down at a 11. Kaiya H: Second messenger imbalance hypothesis of schizo- rate that was significantly greater than normal and phrenia. Prostaglandins Leukotrienes Essential Fatty Acids this finding further suggested that there may be some- 12. Pletscher A: Liberation of catecholamines from blood plate- thing faulty about the platelets themselves. A subse- quent nonspecific antibody study revealed that ‘‘some 13. Essali MA, Das I: Regulation of the platelet phosphoinositide antibody in both the patient’s plasma and attached system by antipsychotic drugs: A specific neuroleptic action.
Schizophrenia Res 1990; 3:36–37 to his platelets was capable of destroying donor plate- 14. Kaiya H, et al.: Accumulation of diacylglycerol in platelet lets, suggesting that antibodies were being produced phosphotidylinositide turnover in schizophrenia: A biological in response to a non specific antigen’’ (4). These marker of good prognosis? Biol Psychiatry 1989; 26:669–676 15. Loiseau P: Sodium valproate, platelet dysfunction, and bleed- authors believed that the antigen substance is usually a drug, which in their case was narrowed down to 16. Tohen M, et al.: Blood dyscrasia with carbamazepine and chlorpromazine. Their literature survey concluded valproate: A pharmacoepidemiological study of 2,228 patientsat risk. Am J Psychiatry 1995; 152:413–418 that phenothiazines with an aliphatic side chain, such 17. Vadney V: Unusual clusters of valproate-associated thrombo- as chlorpromazine, or with a piperadine side chain,


Microsoft word - miralax[1].doc

In order for the doctor to perform a colonoscopy, a bowel “cleanout” must be completed at home prior to the procedure. A bowel cleanout is a combination of a clear liquid diet and oral laxatives. The doctors prefer using NuLytely/GoLytely, it is the most effective and safe laxative for cleaning out the colon for better visual results when your procedure is being performed. There are 3 other o

FACULTY GUIDELINES FOR ACCOMMODATING STUDENT RELIGIOUS OBSERVANCES When planning courses, departmental programs, and other activities for the academic year, it is useful to remember the rich mixture of religious and ethnic groups that comprise our student population. The following list includes some religious holy days, civic holidays and festivals that occur during the academic year, vario

Copyright © 2010-2014 Drugstore Pdf Search