M. Pai

Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments.

Summary.  Background: Light transmission aggregometry (LTA) is commonly performed to assess individuals for bleeding disorders. Objectives: The goal was to evaluate the incidence and spectrum of platelet function abnormalities in a prospective cohort of individuals referred for bleeding disorder assessments after exclusion of thrombocytopenia and von Willebrand disease. Patients/methods: Subjects were healthy controls and patients from a prospective cohort of individuals referred for bleeding disorder assessments after exclusion of thrombocytopenia and von Willebrand disease. LTA was performed by standardized methods using platelet‐rich plasma adjusted to 250 × 109 platelets L−1. Maximal aggregation data were analyzed to determine the likelihood of detecting a platelet function disorder by LTA, and the sensitivity and specificity of LTA for platelet disorders. Results: The incidence of false positive LTA among subjects excluded of having bleeding disorders was similar to healthy controls. Abnormal LTA was more common in subjects with bleeding disorders and the likelihood of a bleeding disorder was significantly increased (odds ratio 32) when maximal aggregation was reduced with two or more agonists. Receiver operator curve analyses indicated that LTA had high specificity and moderate sensitivity for detecting inherited defects in platelet function and that the LTA agonists 1.25 μg mL−1 collagen, 6 μM epinephrine, 1.6 mM arachidonic acid and 1.0 μM thromboxane analogue U44619 detected most inherited disorders with abnormal LTA. Conclusions: LTA is valuable for detecting platelet function abnormalities among individuals referred for bleeding problems, particularly when the test indicates abnormal responses to multiple agonists.

Comparing bleed frequency and factor concentrate use between haemophilia A and B patients

Summary.  Haemorrhagic manifestations in patients with haemophilia A and B are considered quite similar for comparable level of factor deficiency. We investigated the bleeding frequency and factor usage between HA and HB patients with comparable disease severities. We collected data on frequency of bleeds and factor concentrate utilization over 3 years, from January 2001 to December 2003. Information was gathered from home infusion logs recorded by patients or their parents, and treatment records from the Hemophilia Clinic or the Hospital Emergency Department. Data were available on 58 patients with severe HA (FVIII < 0.01 U mL−1), 10 with moderate HA (FVIII < 0.05 U mL−1), 15 with severe HB, and five with moderate HB who required treatment for episodic bleeds, postoperative haemostasis and for primary or secondary prophylaxis. The HA patients bled more frequently than HB patients (14.4 vs. 8.63 bleeds/patient/year), but used similar amounts of concentrate per year. HA patients underwent surgical procedures 3.2 times more frequently than HB patients to correct musculoskeletal complications. A total of 21 363 409 IU of recombinant FVIII was used by patients with HA (104 722 IU/patient/year) and 6 430 960 IU of recombinant factor IX, by patients with HB (107 182 IU/patient/year). The difference in factor concentrate usage is not statistically significant (P > 0.05). The decrease in bleed frequency in haemophilia B indicates that the conclusions from randomized trials of prophylaxis in HA may not be accurately applied to HB.

Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study.

Essentials Heparin‐induced thrombocytopenia (HIT) is a thrombogenic condition that is difficult to treat. We evaluated rivaroxaban as a treatment option in patients with suspected or confirmed HIT. One patient had recurrent thrombosis and 9/10 patients with thrombocytopenia had platelet recovery. Rivaroxaban may be an effective and safe treatment option for HIT.

Diagnosis and treatment of intracranial hemorrhage in children with hemophilia.

Intracranial hemorrhage (ICH) is a significant complication for children with hemophilia. Identifying risk factors may allow us to establish clinically relevant guidelines for the diagnosis and management of ICH. The purpose of this review is to nucleate evidence from the available literature on the incidence, risk factors, presentation, treatment, and outcomes of ICH that can be utilized to develop a clinically useful framework for the diagnosis and management of hemophiliac patients with the condition. An electronic MEDLINE and EMBASE literature search was undertaken using the key words ‘intracranial hemorrhage and hemophilia’ and setting limits as: Last 10 years and Review or Randomized Controlled Trial (RCT) or Clinical Trial, or Practice Guidelines. Following review of all articles using predetermined search words and criteria, 31 were retrieved with sufficient data to address our objectives. An algorithm is presented for the management of children (≥3 years–18 years) with hemophilia and suspected ICH. A standardized approach to ICH may reduce unnecessary exposure to radiation via computed tomography scan in a select group of children. Currently there is limited scientific evidence to recommend a diagnostic and therapeutic algorithm for neonates with hemophilia.

Shock, acute disseminated intravascular coagulation, and microvascular thrombosis: is 'shock liver' the unrecognized provocateur of ischemic limb necrosis?

For unknown reasons, a small minority of critically ill patients with septic or cardiogenic shock, multiorgan failure, and disseminated intravascular coagulation develop symmetrical acral (distal extremity) limb loss due to microvascular thrombosis (‘limb gangrene with pulses’). Case reports have described preceding ‘shock liver’ in some critically ill patients who developed such a picture of ischemic limb necrosis. This suggests that profoundly disturbed procoagulant–anticoagulant balance featuring uncontrolled generation of thrombin—resulting from failure of the protein C and antithrombin natural anticoagulant systems due to insufficient hepatic synthesis of these crucial proteins—could explain the microvascular thrombosis and associated limb loss. We hypothesize that shock liver is the key predisposing risk factor underlying ischemic limb necrosis in the majority of patients who develop this complication in the setting of acute disseminated intravascular coagulation complicating septic or cardiogenic shock. As shock liver precedes onset of limb ischemia by several days, therapeutic intervention may be possible.

Selective IgA Deficiency in Rh-Negative Women

Abstract. Sera obtained from 15,500 Rh‐negative pregnant women were screened for presence of serum IgA. 12 out of 15,500 or 0.08% of the women were deficient in serum IgA, and only one of these 12 women had anti‐IgA antibody of broad specificity. Nine women with IgA deficiency received anti‐Rho γ‐globulin within 72 h after delivery. None of them developed anti‐IgA antibodies 3–6 months following injection of anti‐Rho γ‐globulin. Administration of Rh immune globulin to one subject (case No. 5) in this group who has class‐specific anti‐IgA was not associated with any untoward reactions, and there was no significant change in the antibody level.

Developing a tracking system for coagulation factor concentrates in southern Ontario

BACKGROUND : In response to the transfusion‐ transmitted AIDS epidemic, Canadian authorities rec‐ ommended the development of tracking systems and improved reporting of adverse events. This study describes the development of a verifiable and comprehensive regional tracking system for coagulation factor concentrates.

Trends in the utilization and wastage of coagulation factor concentrates: the application of a regional tracking programme

Summary.  The Commission of Inquiry on the Blood System in Canada (‘Krever Commission’, 1997) recommended an active programme of surveillance for all blood products. To describe trends in the utilization of coagulation factor concentrates using a comprehensive factor tracking programme. Between 2001 and 2004 in the region of Southern Ontario, we prospectively tracked all coagulation factor concentrates that were distributed from the national blood supplier, issued by hospitals for inpatient use or for home infusions, infused at hospital facilities or at home and wasted. Discrepancies were reconciled by independent audits. Trends in the utilization of FVIII, FIX and FVIIa concentrates are reported. A total of 466 patients with inherited or acquired bleeding disorders were registered. Utilization of FVIII, FIX and FVIIa increased by an average of 13.7%, 33.2% and 34.2% per year respectively. Most FVIII and FIX infusions were administered at home while most FVIIa infusions were in hospital. The increase in FVIII and FIX usage was attributable to an increase in per‐patient use, predominantly for prophylaxis. In total, 1.7% of coagulation factor concentrates was wasted during the study period, at a cost of over 1 million Canadian dollars. Utilization of coagulation factor concentrates increased steadily during the study period. A regional programme to track utilization is feasible and may be used to describe trends, assist planning, and reduce costs by minimizing wastage.

Group O RBCs: where is universal donor blood being used

There have been recurrent shortages of group O blood due to insufficient inventory and use of group O blood in ABO non‐identical recipients. We performed a 12‐year retrospective study to determine utilization of group O Rh‐positive and Rh‐negative red blood cells (RBCs) by recipient ABO group. Reasons for transfusing group O blood to ABO non‐identical recipients were also assessed.

Utilization of recombinant activated factor VII in southern Ontario in 85 patients with and without haemophilia

Summary.  Recombinant activated factor VII (rFVIIa) is licensed for the treatment of bleeding in individuals with haemophilia and inhibitors. The use of rFVIIa appears to be increasing, and an increase in unlicensed use is suspected. There are currently few data about the specific indications for its use.