Thrombocytopenia and drugs

Thrombocytopenia is a relatively common side effect of drug therapy. The pathogenetic mechanisms of drug-induced thrombocytopenia are varied and sometimes poorly understood. Immunologic and other cytotoxic effects may result in decreased production and/or increased destruction of platelets. The pathogenesis of drug-induced thrombocytopenia is reviewed. Diagnosis and treatment are also discussed.     

质粒介导喹诺酮类耐药机制研究进展

质粒介导喹诺酮类耐药(PMQR)基因的出现,迅速提高了细菌对喹诺酮类药物的耐药性,给临床细菌性疾病的治疗带来了严重的威胁。目前虽然认为喹诺酮类耐药基因(qnr)只引起低水平耐药,但低水平耐药性可使细菌数量达到出现突变所需的浓度,从而出现高水平耐药。因此,对质粒介导该类药物耐药机制的研究,及耐药基因的分子传播机制的研究不仅能指导临床合理用药,而且有助于控制耐药菌株的产生和传播。     

Concurrent bartonellosis and babesiosis in a dog with persistent thrombocytopenia

A 12-year-old castrated male West Highland White Terrier was referred because of recurrent episodes of collapsing. The dog was mildly anemic and severely thrombocytopenic and had high serum alanine aminotransferase activity. Infection with Bartonella vinsonii (berkhoffii) was initially diagnosed on the basis of serologic testing. Despite treatment with a series of antimicrobials and prolonged use of immunosuppressive drugs, thrombocytopenia persisted. After 5 months of treatment, Babesia canis organisms were seen during examination of a direct blood smear. The dog was treated with imidocarb dipropionate for babesiosis, after which thrombocytopenia resolved, and administration of immunosuppressive drugs was discontinued. Retrospective review of blood smears failed to identify organisms; however, polymerase chain reaction (PCR) analysis of multiple stored blood samples obtained during the 5-month period of persistent thrombocytopenia identified DNA of B. canis vogeli. Babesiosis may cause persistent, unexplained thrombocytopenia in dogs that are not anemic. A PCR assay can facilitate a diagnosis of babesiosis when organisms are not evident or when serologic testing fails to detect Babesia-specific antibodies.     

Resolution of severe thrombocytopenia in two standard Poodles with surgical correction of splenic torsion

Objective: To describe the diagnosis and treatment of 2 cases of severe thrombocytopenia associated with splenic torsion and to discuss the pathophysiologic mechanisms underlying the thrombocytopenia. Summary: We report 2 cases of severe thrombocytopenia associated with splenic torsion. Each dog presented with non‐specific clinical signs, radiographic evidence of an intra‐abdominal mass, and platelet counts of less than 25,000 platelets/μL. The diagnosis of splenic torsion was made with abdominal ultrasonography and was confirmed during exploratory laparotomy. Both dogs recovered rapidly following splenectomy. The cause of thrombocytopenia associated with splenic torsion is not fully elucidated, but may be because of either platelet sequestration within the torsed spleen, platelet consumption in disseminated intravascular coagulation, or a combination of both. New information provided: This report provides previously unreported evidence that the degree of thrombocytopenia associated with splenic torsion may be of a severity at which primary hemostasis is compromised, and resolution of thrombocytopenia occurs after splenectomy.     

African swine fever and classical swine fever: a review of the pathogenesis

This paper describes major pathogenetic mechanisms of African and Classical Swine Fever virus infections. The interactions between both viruses and the monocyte-macrophage-system result in the release of mediator molecules, which are important for the further progression of the diseases. The causes of the thrombocytopenia and the mechanisms of the haemorrhages, which are characteristic in both infections, are described. Apoptotic cell death is regarded as the predominant cause of lymphopenia in both virus infections.     

Thrombosis of the caudal vena cava presenting as an unusual cause of an abdominal mass and thrombocytopenia in a dog

Thrombosis of the caudal vena cava in a dog secondary to metastatic neoplasia is described. The dog had a palpable abdominal mass and persistent thrombocytopenia due to a thrombosed caudal vena cava that was surgically removed. A few days after its removal, the dog died and neoplastic cells of neural crest origin were identified at the edge of the thrombus. Massive thrombosis can be an unusual cause of platelet consumption, leading to thrombocytopenia and disseminated intravascular coagulation. Deep vein thrombosis of the vena cava can occur in dogs and may mimic an abdominal mass. Multiple mechanisms may be involved in the development of venous thrombosis, including endothelial damage by neoplastic cells and the presence of a hypercoagulable state secondary to neoplasia. Extensive collateral circulation may allow removal of diseased vena cava.     

锥虫抗药性的原因与机制研究进展

通过对锥虫抗药性形成的原因、影响因素以及抗药性的遗传稳定性等方面的阐述,进而揭示锥虫抗药性形成的机制。目前的研究结果表明,锥虫抗药机制主要有3点：通过虫体酶活性的变化而影响虫体对药物的敏感性,虫体对腺苷酸等物质的吸收抑制药物对虫体的溶解作用,以及虫体抗药基因的活化。     

Immune evasion and immunosuppression by Anaplasma phagocytophilum, the causative agent of tick-borne fever of ruminants and human granulocytic anaplasmosis

Anaplasma phagocytophilum, the causative agent of tick-borne fever (TBF) in sheep and cattle and human granulocytic anaplasmosis, has the unique ability to infect and multiply within neutrophils, eosinophils and monocytes, cells at the frontline of the immune system. Infection with A. phagocytophilum is also characterized by severe leukopenia due to lymphocytopenia, neutropenia and thrombocytopenia lasting for several days. By itself TBF does not cause high mortality rates but infected animals are more susceptible to other secondary infections, pregnant animals may abort and there is a severe reduction in milk yield in dairy cattle. The susceptibility to secondary infections can be attributed to the leukopenia that accompanies the disease and the organism's adverse effects on lymphocyte and neutrophil functions. One of its fascinating features is that it infects and actively grows in neutrophils by employing an array of mechanisms to subvert their bactericidal activity. These include its ability to inhibit phagosome-lysosome fusion, to suppress respiratory burst and to delay the apoptotic death of neutrophils. It is also able to survive within an apparently immune host by employing a complex mechanism of antigenic variation.     

Equine endotoxaemia--a state-of-the-art review of therapy

The pathophysiology of endotoxaemia, a leading cause of death in the horse, is beginning to be understood in greater detail. Endotoxin may be absorbed into the systemic circulation in a number of different ways: most commonly the body's normal defense mechanisms are disrupted or bypassed, or the normal clearance mechanisms overwhelmed. Following this wide-spread effects are observed, although the most significant are seen in the cardiovascular system. Fever, arterial hypoxaemia and signs of abdominal pain are also common. With increased understanding of the disease new therapeutic agents have become available, however, while the newer agents offer some advantages it is important to recognise that supportive care is the mainstay of treatment for endotoxaemia. Supportive care consists of aggressive fluid therapy (crystalloid, colloid and hypertonic), the administration of non-steroidal antiinflammatory drugs and, where appropriate, antimicrobials. The principles of supportive care are discussed in detail. Other therapies such as hyperimmune plasma, polymyxin B, pentoxifylline, dimethyl sulfoxide and heparin are commonly used in the treatment of equine endotoxaemia and their use is reviewed here. Furthermore, newer agents such as anti-tumour necrosis factor antibodies, detergent, activated protein C and insulin, which have yet to gain widespread acceptance but may have an important role in the treatment of endotoxaemia in the future, are examined.     

Flow cytometric detection of platelet-bound antibody in three horses with immune-mediated thrombocytopenia

Immune-mediated thrombocytopenia (IMT) is a sporadic cause of thrombocytopenia in horses for which it is difficult to establish a definitive diagnosis. In this report, we describe 3 horses with severe thrombocytopenia in which flow cytometric analysis of platelets for surface-bound IgG was used in an attempt to substantiate a provisional diagnosis of IMT. A distinct proportion (4.28%, 5.04%, and 7.95%) of platelets with surface-bound IgG was detected in the 3 thrombocytopenic horses, but not in 6 healthy horses (0.03% to 0.15%) or 6 horses with colic (0.00% to 1.21%). These results, in conjunction with elimination of other potential causes of the thrombocytopenia, established a diagnosis of IMT. The horses were treated with glucocorticoids alone or in combination with azathioprine, and the thrombocytopenia gradually resolved. Flow cytometric detection of platelet-bound IgG was readily performed and may be a useful adjunct for the diagnosis of IMT.     

A veterinary perspective on methicillin-resistant staphylococci

Objective – To familiarize the reader with the epidemiology, diagnosis, and infectious and zoonotic potential of methicillin-resistant staphylococci.
Data sources – Original research publications, scientific reviews and abstracts, case reports, and conference proceedings.
Human Data Synthesis – Staphylococcus aureus is a common human commensal organism; acquisition of genes encoding an altered penicillin-binding protein confers resistance to β-lactam antimicrobial drugs. Methicillin-resistant S. aureus (MRSA) are often resistant to non–β-lactam antimicrobial drugs as well. Originally described as an important cause of nosocomial infection, MRSA colonization and infection are now often identified in humans outside healthcare settings. Like other S. aureus , MRSA may be present without clinical illness. However, when they do cause infection the consequences can be extremely serious.
Veterinary Data Synthesis – The major domestic animal species, including pets and livestock, may become contaminated, colonized, or infected with methicillin-resistant staphylococci, including MRSA. Dogs and cats are more likely to be colonized/infected with Staphylococcus pseudintermedius than S. aureus , but this pathogen can acquire genes encoding methicillin resistance (ie, MRSP). Diagnosis of MRSA or MRSP has implications not only for treatment of infected animals, but for potential zoonotic transmission.
Conclusions – MRSA infection is an important cause of morbidity and mortality in humans. Animals may be contaminated, colonized, or infected with MRSA, with implications for the animal's health and as a potential reservoir for human infection. Staphylococci other than S. aureus may also acquire genes for methicillin resistance, and these species can also result in animal and occasionally human morbidity or mortality.     

Presumed primary immune-mediated thrombocytopenia in four cats

Feline primary immune-mediated thrombocytopenia (pIMT) is a rare hematological disorder. Platelet-bound antibody assays for cats have variable specificity and sensitivity and are not widely available. Diagnosis of pIMT is made on the basis of exclusion of other identifiable causes of thrombocytopenia and the response to immunosuppressive therapy. This report describes four cats with severe thrombocytopenia and no detectable underlying disease. One cat was euthanased because of pulmonary hemorrhage, while the other cats had frequent relapses, two of these cats developed diabetes mellitus due to long-term corticosteroid therapy. In these cats IMT had a chronic course and responded poorly to therapy with prednisolone. Alternative immunomodulatory drugs may be considered in the treatment of feline IMT.     

Part 1: Treatment of Snial Bait Toxicity in Dogs: Literature Review

Metaldehyde and methiocarb are two snail baits (molluscicides) which are commonly ingested by dogs and cause rapid onset of severe neurological symptoms. Rapid and appropriate treatment is essential for patient survival. This paper summarizes the literature on treatment of metaldehyde and methiocarb toxicity, based primarily on actual case reports from the past 35 years.
There are important differences between metaldehyde and methiocarb in their mechanisms and treatment. Metaldehyde's mechanism is unknown; methiocarb is a carbamate and parasympathomimetic. Pentobarbitone anesthesia and atropine have been the mainstays of treatment in metal-dehyde and methiocarb toxicity, respectively; their limitations and disadvantages are discussed. Other drugs and aspects of treatment, such as acetylpromazine, diazepam, gastric lavage, and hypetihermia, are also discussed.
Clinical signs are similar in both types of toxicity, but treatment may be complicated by the development of hyperthermia and atropine poisoning which also have similar clinical signs.     

Acute pancreatitis in two dogs given azathioprine and prednisone

Acute pancreatitis was diagnosed in 2 dogs given azathioprine and prednisone. Prednisone and azathioprine had been given as immunosuppressive therapy for pemphigus foliaceus in dog 1 and for polymyositis in dog 2. Azathioprine was discontinued in both dogs. In dog 1, prednisone was reinstituted on day 6 of hospitalization. Prednisone was continued throughout the period of hospitalization in dog 2. Both dogs recovered without complication. Glucocorticoid therapy has been associated with the development of pancreatitis. In human beings, a common side effect of azathioprine is the development of drug-induced pancreatitis. Definitive identification of azathioprine as the cause of pancreatitis in these dogs was not possible; the owners refused to permit retreatment with the drug. Therefore, the synergistic action between these 2 drugs could not be ruled out as the cause of pancreatitis.     

Adverse drug interactions of importance in veterinary practice

Multiple drug therapy is often used in veterinary practice; occasionally, inappropriate combinations of drugs may be administered which interact to produce adverse responses. Such interactions may occur in vitro because of physically or chemically incompatible drugs having been mixed before administration or in vivo. A number of important in vitro incompatibilities concerning parenteral drugs are tabulated, consideration having been given both to problems attending the use of intravenous fluids as vehicles for their administration and to incompatibilities between the drugs themselves. Interactions which occur in vivo are also examined; these have been grouped according to the various mechanisms by which they occur.     

Detection of platelet-bound antibodies in beagle dogs after artificial infection with Ehrlichia canis

Six dogs were infected with Ehrlichia canis by intravenous injection of heavily infected DH82 cells. All dogs developed typical signs of canine monocytic ehrlichiosis. Using flow cytometric technology, platelet-bound IgG (PBIgG) were detected in 5 of the 6 dogs after experimental infection with E. canis over a period of 3-10 days post infection (PI). The first detection of PBIgG was made as early as day 3 PI in 2 out of 6 dogs, and on day 5 PI in 1 dog. On day 7 PI, PBIgG was detected in 2 dogs, and on day 10 PI in 3 out of 6 dogs. This is the first report documenting the presence of PBIgG following E. canis infection in dogs. This finding further supports the theory that the thrombocytopenia seen in canine monocytic ehrlichiosis has an immunological component and that exposure to an infectious agent, in this case the rickettsia E. canis, can trigger autoimmune mechanisms. Due to the heterogeneous appearance of PBIgG among the infected dogs it was concluded that other non-immunological mechanisms are probably also involved in the pathogenesis of the thrombocytopenia seen in canine monocytic ehrlichiosis.     

Strategies for management of recurrent pyoderma in dogs

Staphylococcal skin infection (pyoderma) is a common clinical problem in dogs. The infection can be either superficial or deep. Most cases of staphylococcal pyoderma occur secondary to a definable underlying cause. Treatment consists of finding the underlying cause and correcting it, if possible, and treating the pyoderma with antibiotics. Antibacterial shampoos may be used as adjunct treatment, but corticosteroid drugs should not be used. When canine pyoderma recurs in the absence of an identifiable underlying cause, several treatment strategies can be effective in eliminating recurrence or limiting its severity. Frequent antibacterial shampoos are an easy and sometimes effective method. Immunomodulatory drugs are variably effective. Some commercially available bacterins are clearly helpful in treating recurrent pyoderma. As a last resort, the clinician may opt to keep the patient on long-term antibiotic therapy. Such therapy may promote development and dissemination of resistant strains of Staphylococcus and should be used only if absolutely necessary.     

Thrombocytopenia associated with vaccination of a dog with a modified-live paramyxovirus vaccine

Thrombocytopenia (10,000/mm3), with hematochezia and melena, appeared in a dog 8 days after it was given modified-live canine distemper, virus vaccine and persisted for approximately 5 days. Clinical investigation discounted other possible causes of thrombocytopenia; the condition was considered to be associated with vaccination. The problem spontaneously resolved. The appearance of thrombocytopenia after modified-live canine distemper virus vaccination is not unknown and may assume a severe form. This condition may be mistaken for idiopathic thrombocytopenia of immune origin, and in other instances, it may contribute significantly to surgical risk if concurrent coagulation disorders are present. Administration of levamisole HCl may alleviate the decrease in platelet count in affected animals.     

Pseudothrombocytopenia secondary to the effects of EDTA in a dog

Pseudothrombocytopenia (PTCP) secondary to the effects of ethylenediaminetetraacetic acid (EDTA) has been noted in horses and pigs and should be considered in dogs with moderate thrombocytopenia and no clinical bleeding tendency. This type of pseudothrombocytopenia is not a pathological process by itself, but it can be clinically significant if diagnostics and medical treatments are initiated based on the reported thrombocytopenia. Platelet clumping occurs with EDTA-dependent PTCP, resulting in inaccurate hematology analyzer platelet concentrations. A nontraumatic venipuncture may be sufficient to obtain an accurate platelet count. However, rare cases in the dog may require blood drawn into a different anticoagulant, such as sodium citrate, to help discriminate a true thrombocytopenia from PTCP.     

畜禽氧化应激与炎症及多酚的干预作用

氧化应激是畜禽体内活性氧产生与保护机制消除的失衡,可导致组织产生氧化损伤,最终诱发炎性疾病。氧化应激可激活多种转录因子,导致炎症途径相关基因的差异表达,由氧化应激引起的炎症是许多慢性疾病的病因。多酚作为植物次生代谢产物,被认为是有效的辅助治疗佐剂,在人和动物中发挥潜在的抗氧化和抗炎作用。多酚也被认为是具有应用潜力的畜禽饲料添加剂。综述了畜禽氧化应激与炎症的关系及机制、多酚对畜禽的抗氧化和抗炎作用及机制,以期为动物疾病抗氧化疗法的应用和新型抗炎药物的开发提供参考。