INDEXES OF CYTOKINE PROFILE OF BLOOD IN PATIENTS WITH COMPLICATED ERYSIPELAS.

The cytokine blood profile in patients with complicated erysipelas was investigated. It was found that in patients with complications of erysipelas (gangrene, phlegmon, abscess, thrombophlebitis of the subcutaneous veins of the shin) levels of pro-inflammatory cytokines IL-1ß, TNF-α, IL-2, IL-6 in serum significantly increase and level of anti-inflammatory cytokine IL-4 increases slightly, as well as was found a significant increase in coefficients reflecting the ratio of pro-inflammatory and anti-inflammatory cytokines, which indicates the prevalence in the blood of examined patients with complications of erysipelas an anti-inflammatory properties. A more significant increase in pro-inflammatory cytokines serum levels is typical for patients with destructive forms of erysipelas - phlegmonous and gangrenous, a slight increase - for patients without purulent-necrotic component of complication (thrombophlebitis of the subcutaneous veins of the shin). In the future we plan to study pharmacological correction of shifts in cytokine blood profile with drugs with immunomodulating properties in patients with complicated erysipelas.

Spontaneous HIT syndrome post-knee replacement surgery with delayed recovery of thrombocytopenia: a case report and literature review.

Recently published reports have established a heparin-induced thrombocytopenia (HIT)-mimicking thromboembolic disorder without proximate heparin exposure, called spontaneous HIT syndrome. Although the pathophysiology remains unclear, anti-platelet factor 4 (PF4)/heparin antibodies possibly triggered by exposure to knee cartilage glycosaminoglycans or other non-heparin polyanions found on bacterial surfaces and nucleic acids have been postulated. We present a 53-year-old female receiving antithrombotic prophylaxis with aspirin following right total knee replacement surgery (without perioperative or any previous lifetime heparin exposure) who acutely presented with high-risk pulmonary embolism (PE) and right great saphenous vein thrombophlebitis on postoperative day (POD) 14; her platelet count at presentation was 13 × 109/L. Prior to diagnostic consideration of spontaneous HIT syndrome, the patient briefly received unfractionated heparin (UFH) and one dose of enoxaparin. The patient's serum tested strongly positive for anti-PF4/heparin antibodies by two different PF4-dependent enzyme-linked immunosorbent assays (ELISAs) and by serotonin release assay (SRA). Failure of fondaparinux anticoagulation (persisting HIT-associated disseminated intravascular coagulation) prompted switching to argatroban. Severe thrombocytopenia persisted (platelet count nadir, 12 × 109/L, on POD21), and 9 days after starting argatroban symptomatic right leg deep-vein thrombosis (DVT) occurred, prompting switch to rivaroxaban. Thereafter, her course was uneventful, although platelet count recovery was prolonged, reaching 99 × 109/L by POD45 and 199 × 109/L by POD79. The patient's serum elicited strong serotonin release in the absence of heparin (seen even with 1/32 serum dilution) that was enhanced by pharmacological concentrations of UFH (0.1 and 0.3 IU/mL) and fondaparinux (0.1-1.2 µg/mL, i.e., in vitro fondaparinux "cross-reactivity"). Ultimately, platelet count recovery was associated with seroreversion to a negative SRA (documented at POD151). Our literature review identified joint replacement surgery, specifically knee replacement, to be a relatively common trigger of spontaneous HIT syndrome. Further, including our patient case, 5 of 7 patients with spontaneous HIT syndrome post-orthopedic surgery who received treatment with argatroban developed new and/or progressive lower-limb DVT or recurrent PE despite anticoagulation with this parenteral direct thrombin inhibitor, suggesting that this patient population is at high risk of breakthrough thrombotic events despite treatment with this HIT treatment-approved anticoagulant. Our case also illustrates successful outcome with rivaroxaban for treatment of spontaneous HIT syndrome, consistent with emerging literature supporting safety and efficacy of direct oral anticoagulant therapy for treatment of acute HIT.

Predicting and preventing thromboembolic events in patients receiving cisplatin-based chemotherapy for germ cell tumours.

BACKGROUND: Patients with germ cell tumours (GCT) receiving cisplatin-based chemotherapy are at high risk of thromboembolic events (TEE). Previously, we identified serum lactate dehydrogenase (LDH) and body surface area (BSA) as independent predictive factors for TEE. The aim of this study was to validate these predictive factors and to assess the impact of thromboembolism prophylaxis in patients at risk of deep venous thrombosis (DVT). METHODS: Between 2001 and 2014, 295 patients received first-line cisplatin-based chemotherapy for GCT. Preventive anticoagulation with low-molecular-weight heparin (LMWH) was progressively implemented in patients with predictive factors. Sixteen patients with evidence of TEE before starting chemotherapy were excluded from the analysis. RESULTS: Among 279 eligible patients, a TEE occurred in 38 (14%) consisting of DVT (n = 26), arterial thrombosis (n = 2), and superficial thrombophlebitis (n = 10). DVT occurred in 26 (12.7%) of 204 patients with risk factors versus two (2.6%) of 75 patients with no risk factors (p = 0.01). After a prevention protocol was progressively implemented from 2005, primary thromboprophylaxis was administered to 104 patients (68%) with risk factors. Among patients at risk (n = 151), the incidence of DVT decreased by roughly half when they received a LMWH: 9/97 (9.2%) and 9/54 (16.6%), respectively (p = 0.23). CONCLUSION: Patients with GCT who receive cisplatin-based chemotherapy are at risk of developing a TEE which can be predicted by elevated serum LDH. To our knowledge this is the first study exploring LMWH as thromboprophylaxis in GCT patients. A prospective trial testing prophylactic anticoagulation is warranted.

[NHG guideline 'Deep-vein thrombosis and pulmonary embolus']. / NHG-standaard 'Diepe veneuze trombose en longembolie'.

The revised Dutch College of General Practitioners (Nederlands Huisartsen Genootschap [NHG]) guideline 'Deep-vein thrombosis and pulmonary embolus' includes recommendations for the treatment of patients with deep-vein thrombosis (DVT) and thrombophlebitis, and for the exclusion of pulmonary embolism (PE). The general practitioner (GP) can exclude the presence of DVT or PE in some patients by using a decision rule and a D-dimer test. When using D-dimer test as a point-of-care test, meticulous care is essential during the test procedure and storage of blood. The GP can treat many patients with DVT; the NHG guideline does not advise use of direct oral anticoagulants. In the case of an isolated DVT in the calf, treatment with anticoagulants or ultrasound follow-up can be chosen in consultation with the patient or on the basis of regional agreements. In the case of patients with superficial thrombophlebitis, a wait-and-see approach is usually sufficient.

The association of haemoglobin A1C levels with the clinical and CT characteristics of Klebsiella pneumoniae liver abscesses in patients with diabetes mellitus.

OBJECTIVES: To compare the characteristics of Klebsiella pneumoniae liver abscesses (KPLA) in diabetic patients with different levels of glycaemic control. METHODS: The institutional review board approved this retrospective study. A total of 221 patients with KPLA were included. Clinical features of KPLA were compared. We divided the 120 diabetic patients with KPLA into three subgroups based on haemoglobin A1C (HbA1C) concentration (good, HbA1C ≤ 7.0 %; suboptimal, 7.0 % < HbA1C ≤ 9.0 %; poor, HbA1C > 9.0 %). In this study, we used a semiautomated quantitative method to assess the gas and total abscess volumes in KPLA. Statistical analysis was performed with the chi-squared test and one-way analysis of variance. RESULTS: The mortality rate did not significantly differ between the nondiabetic and diabetic groups. However, patients with poor glycaemic control had significantly more complications and therefore a longer hospital stay (P < 0.05). In our study, CT and quantitative analyses found that patients in the group with poor glycaemic control had a significantly higher incidence of gas formation and hepatic venous thrombophlebitis and a higher gas-to-abscess volume ratio than patients with suboptimal and good glycaemic control (P < 0.05). CONCLUSIONS: Diabetic patients with a high HbA1C concentration (>9.0 %) have an association with hepatic venous thrombophlebitis, gas formation and metastatic infection complications associated with KPLA. KEY POINTS: • Poorly controlled diabetes is associated with complications in Klebsiella pneumoniae liver abscesses. • Hepatic venous thrombosis and gas are important signs of metastatic infection. • Hepatic venous thrombophlebitis is associated with 72.7 % of metastatic infections.

[Post-varicella cerebral thrombophlebitis with anti-protein S: report of a pediatric case]. / Thrombophlébite cérébrale post-varicelle avec anticorps anti-protéine S : à propos d'un cas pédiatrique.

Purpura fulminans and venous thrombosis are rare complications of chickenpox. We report the case of a 6 year old with no history individuals who experienced cerebral thrombophlebitis, 3 weeks after varicella. MRI, performed at admission, has objectified longitudinal sinus thrombosis and a frontal parenchymal hematoma law. Meanwhile, a recent varicella seroconversion was demonstrated. The assessment of thrombophilia, meanwhile, has objectified a significant decrease in free protein S and activity, without associated DIC. Origin acquired this deficit was confirmed by the detection of antibodies (IgG and IgM) against the total protein S by ELISA. After evaluation of the benefit/risk only anticoagulation was initiated. The clinical and biological evolution was favorable, with rapid normalization of the S protein and decrease of anti-protein S. Many studies report the presence of anti-protein S in young children at the waning of chickenpox, without their exact frequency is determined. The decrease in protein S they cause leads to a transient hypercoagulable state may result in different clinical pictures. Cases of purpura fulminans seem more frequent when venous thrombosis isolated post chickenpox, sometimes atypical, appear rare.

Early ultrasonographic finding of septic thrombophlebitis is the main indicator of central venous catheter removal to reduce infection-related mortality in neutropenic patients with bloodstream infection.

BACKGROUND: Septic thrombophlebitis increases patient morbidity and mortality following metastatic infections, pulmonary emboli, and/or septic shock. Central venous catheter (CVC) removal for occult septic thrombophlebitis challenges current strategy in neutropenic patients. PATIENTS AND METHODS: We prospectively evaluated infection-related mortality in 100 acute leukemia patients, with CVC-related bloodstream infection (CRBSI) after chemotherapy, who systematically underwent ultrasonography to identify the need for catheter removal. Their infection-related mortality was compared with that of a historical cohort of 100 acute leukemia patients, with CRBSI after chemotherapy, managed with a clinically driven strategy. Appropriate antimicrobial therapy was administered in all patients analyzed. RESULTS: In the prospective series, 30/100 patients required catheter removal for ultrasonography-detected septic thrombophlebitis after 1 median day from BSI onset; 70/100 patients without septic thrombophlebitis retained their CVC. In the historical cohort, 60/100 patients removed the catheter (persistent fever, 40 patients; persistent BSI, 10 patients; or clinically manifest septic thrombophlebitis, 10 patients) after 8 median days from BSI onset; 40/100 patients retained the CVC because they had not clinical findings of complicated infection. At 30 days median follow-up, one patient died for infection in the ultrasonography-assisted group versus 17 patients in the historical cohort (P<0.01). With the ultrasonography-driven strategy, early septic thrombophlebitis detection and prompt CVC removal decrease infection-related mortality, whereas clinically driven strategy leads to inappropriate number, reasons, and timeliness of CVC removal. CONCLUSION: Ultrasonography is an easy imaging diagnostic tool enabling effective and safe management of patients with acute leukemia and CRBSI.

Simultaneous appearance of leukemoid reaction and phlegmasia cerulea dolens.

A leukemoid reaction is an extreme form of reactive leukocytosis defined as granulocytic leukocytosis above 50 × 10(9)/L produced by normal bone marrow, mostly in response to systemic infection or cancer. The mechanism as to how the haematopoetic system is altered to elevate production of myeloid cells is not known. A 69-year-old man presented with phlegmasia cerulea dolens caused by massive iliofemoral thrombosis. His workout at admission revealed absolute white blood cell count of 73.4 × 10(9)/L, with neutrophil granulocyte of 68.5 × 10(9)/L. The new increase in white blood cell count happened at day 5 after admission, when the haematoma of the anteromedial thigh was evacuated in general anaesthesia. There was a gradual decrease in counts until they reached the normal range. Deteriorated general condition with signs of systemic inflammatory response syndrome improved with supportive therapy, and the patient was discharged from hospital after 30 days. During hospitalization we did not identify any infectious focus, or any malignancy. We could not exclude other occult chronic conditions (malignancy) but the patient did not develop any other condition during 4.5 years of follow-up.

Platelet activity indices in patients with deep vein thrombosis.

BACKGROUND: Extensive research has been performed regarding the association between platelet activity indices and various cardiovascular disorders. Less clear data, however, are present between these indices and deep vein thrombosis (DVT). AIM: The aim of this study was to investigate the association between platelet activity indices and DVT in a relatively large population. METHODS: Mean platelet volume (MPV), mean platelet mass (MPM), and mean platelet component (MPC) were measured by an autoanalyzer in a total of 203 patients with DVT and the results were compared with 210 age- and sex-matched controls without DVT. RESULTS: There were significant differences between the study and control groups in MPV (8.6 ± 1.3 fL vs 7.9 ± 0.5 fL [95% CI -0.82 to -0.44], P < .001, respectively), MPM (2.2 ± 0.3 pg vs 2.0 ± 0.1 pg [95% CI -0.20 to -0.11], P < .001, respectively), and MPC (24.9 ± 3.2 g/dL vs 26.3 ± 1.6 g/dL [95% CI 0.91 to 1.89], P < .001, respectively). These 3 platelet activity indices were also found to be significant predictors of the presence of DVT (all Ps < .001). CONCLUSION: In patients with DVT, the presence of DVT was closely associated with increased platelet activation. The MPV, MPM, and MPC may identify patients requiring aggressive antiplatelet treatment.

Superficial thrombophlebitis in varicose vein disease: the particular role of methylenetetrahydrofolate reductase.

BACKGROUND: The purpose of this study was to compare the genetic background of superficial (SVT) and deep vein thrombosis (DVT). METHODS: Factor V (FV)-Leiden (G16891A)-, factor II(G20210A)-mutations, protein C- and S, as well as methylenetetrahydrofolate reductase (MTHFR) polymorphisms at C677T and A1298C, and serum homocysteine levels (hcy) were determined in 29 patients with SVT and 26 with DVT. Findings FV- and -II-mutations were less frequent in patients with SVT (2/3) compared with DVT (9/5), respectively (P < 0.002 in case of FV). However, the frequency of the MTHFR C677T polymorphism was significantly higher in patients with SVT compared with DVT (CT 12 versus 10, and TT 7 versus 1, respectively, P << 0.001). The distribution of the MTHFR A1298C genotype and serum hcy levels was similar in both patient groups. Protein S-deficiency was recorded once (SVT). Interpretation These results suggest that the MTHFR C677T-mutant genetically predisposes its carriers to SVT which may contribute to hypercoagulation in pre-existing varicose vein disease.

[Dermatologic aspects of anticoagulation]. / Antikoagulation in der Dermatologie.

The coagulation system protects the body from uncontrolled blood loss by means of highly regulated processes. In case of an injury the coagulation system instantly switches from controlled blood flow to acute coagulation and thrombus formation with the goal of stopping the blood loss. Minor changes in this well-maintained equilibrium of coagulation and blood flow tip the balance towards uncontrolled blood loss or even fatal thromboembolic events. Iatrogenic manipulation of this highly regulated system is possible with a variety of therapeutic agents. We review the basics of coagulation physiology and then discuss dermatologically relevant aspects of thrombosis prevention, as well as the use of anticoagulants to treat dermatologic diseases.

Antiphosphatidylserine-prothrombin complex antibodies in 3 patients with Behçet disease involving superficial vein thrombophlebitis.

BACKGROUND: Superficial vein thrombophlebitis is the common vascular symptom in Behçet disease and is characterized as erythema nodosum-like eruptions. Some studies have reported the presence of antiphospholipid antibodies (Abs) in patients with Behçet disease. OBSERVATIONS: We measured lupus anticoagulant, anticardiolipin, anti-beta(2)-glycoprotein I, and antiphosphatidylserine-prothrombin complex antibody (Ab) levels in 3 patients with Behçet disease involving superficial vein thrombophlebitis. High levels of IgM antiphosphatidylserine-prothrombin complex Abs were found (mean [SD], 50.3 [43.1] U/mL; normal, <10 U/mL). One of the patients with Behçet disease was positive for both IgM and IgG antiphosphatidylserine-prothrombin complex Abs, and 2 were positive for lupus anticoagulant. Two patients were also positive for IgM anticardiolipin Abs, but the titers were low. In contrast, none of the patients with Behçet disease was positive for IgG anticardiolipin Abs or IgG or IgM anti-beta(2)-glycoprotein I Abs. CONCLUSIONS: A high titer of IgM antiphosphatidylserine-prothrombin complex Abs was found in our patients with Behçet disease involving superficial vein thrombophlebitis. We speculate that there is a relationship between the antiphospholipid Abs, especially IgM antiphosphatidylserine-prothrombin complex Abs, and superficial vein thrombophlebitis complications in Behçet disease. This study suggests that elevated serum antiphosphatidylserine-prothrombin complex Ab levels might play some role in the development of the vascular manifestations in Behçet disease.

Effects of acute global venous obstruction and unfractionated heparin on muscle cytokine synthesis.

Phlegmasia cerulea dolens is a devastating complication of massive deep venous thrombosis, which is clinically characterized by massive lower extremity tissue edema and subsequent arterial insufficiency. These experiments evaluated the local tissue effects of acute global venous obstruction combined with partial arterial ischemia. Experiments were performed to assess the effects of heparin on the cytokine response to simultaneous venous and partial arterial obstruction. Murine hind limbs were subjected to conditions of unilateral venous occlusion and partial tourniquet limb ischemia, which was confirmed by laser Doppler imaging (LDI). Mice underwent either hind limb venous obstruction with intravenous unfractionated heparin (200IU/kg) or intravenous saline 5min before venous occlusion. Sham-treated mice were subjected to anesthesia alone without venous occlusion. After 3hr, the mice were killed and tissue was harvested for measurement of edema (wet to dry weight ratio, W/D), muscle viability, indices of local thrombosis (thrombin-antithrombin complex [TAT]), and cytokine analysis for growth-related oncogene-1 (GRO-1) and interleukin-6 (IL-6, protein via enzyme-linked immunoassay and mRNA via reverse transcriptase polymerase chain reaction). Bleeding time and volume were documented in saline- and heparin-treated mice to confirm systemic anticoagulation. Administration of intravenous heparin resulted in a marked increase in bleeding time and volume. LDI confirmed venous obstruction and ongoing arterial inflow. Venous obstruction resulted in severe visible edema that correlated with a significantly higher W/D ratio but was not associated with a significant decrease in muscle viability. GRO-1 and IL-6 protein and mRNA levels were significantly elevated in the venous occlusion group compared to sham. Heparin therapy significantly decreased TAT3 levels but did not alter the profile of GRO-1 or IL-6 protein levels seen with venous occlusion. Venous occlusion with partial ischemia induces a unique and potent local cytokine expression. Heparin therapy did not ameliorate the cytokine response. These data indicate that heparin therapy does not modulate the cytokine response to venous obstruction.