HAU KWAAN, MD

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This is a correction notice for an earlier article on iatrogenic air embolism. It does not contain new findings.

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Patients taking P2Y12 inhibitors (blood thinners like clopidogrel) experienced significantly more bleeding into their brain after intracerebral hemorrhage compared to those not on these drugs, and the effect was even worse when combined with aspirin. The study tracked 194 patients, measuring both drug levels and blood clot sizes on CT scans. This points to P2Y12 inhibitors as an important and underappreciated risk factor for worsening brain bleeds, and raises the question of whether rapidly reversing these drugs could improve outcomes.

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Researchers tested a new contactless ultrasound technique called resonant acoustic rheometry (RAR) to measure how quickly blood plasma clots. RAR detected abnormal clotting in hemophilia A plasma and tracked changes as tissue factor concentration was varied, producing results consistent with standard methods. The technique could eventually offer a simpler, non-contact alternative to existing clot-monitoring devices.

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This is a published reply to a commentary debating whether older-generation viscoelastic clotting tests are still relevant. The authors defend the continued value of legacy devices alongside newer systems. No new clinical data are presented.

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When patients go into shock from any cause, the blood vessel lining becomes damaged, setting off a chain reaction that dysregulates clotting and can lead to organ failure. This review explains the biology behind that process and argues that bedside clot-testing devices (thromboelastography and rotational thromboelastometry) are the best available tools to guide blood product transfusion in real time. Matching treatment to each patient's specific clotting profile can improve survival in trauma, sepsis, and cardiac arrest.

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When air accidentally enters a patient's blood vessels during medical procedures, it triggers an immediate inflammatory and clotting response at the blood vessel lining. The review examines how air bubbles block small vessels, activate the immune system, and cause damage far beyond the initial blockage. Understanding these mechanisms is critical because air embolism is more common than reported, often missed, and requires prompt, targeted treatment.

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Spontaneous intracerebral hemorrhage — bleeding in the brain without a clear trigger — accounts for about a third of all strokes and carries high mortality. Risk factors include age, high blood pressure, and blood-thinning medications, while the size and location of the blood clot and whether it expands after onset are key determinants of outcome. Advances in imaging have improved understanding of why some hematomas grow and how to prevent that growth through blood pressure control and other interventions.

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Viscoelastic hemostatic assays measure the full life cycle of a blood clot using whole blood at the bedside, providing richer information than standard lab tests. This primer compares older devices like TEG5000 and ROTEMdelta to newer cartridge-based and portable systems, explaining what each measures and how they differ. The field has expanded rapidly, with these tests now being adopted across surgery, trauma, and COVID-19 care.

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The fibrinolytic system — the set of proteins that dissolve blood clots — plays essential roles in normal body function including wound healing and cell movement, but also contributes to diseases ranging from cancer to heart disease when it malfunctions. This review maps out the key proteins and inhibitors involved, from plasmin and tPA to PAI-1 and TAFI. A detailed understanding of these pathways is opening new doors for drug development targeting fibrinolysis-related conditions.

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Patients recovering from COVID-19 face higher risks of complications after surgery because the virus disrupts the blood vessel lining and creates an abnormal clotting state that can persist for weeks. The authors propose delaying elective surgery based on each patient's symptom severity, recent illness timeline, and clotting test results. A personalized approach using viscoelastic blood tests and microscopic clot analysis offers the best way to time surgery and manage anticoagulation safely.

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Standard coagulation tests like PT and PTT only capture a small slice of the clotting process and can miss critical problems in actively bleeding patients. Viscoelastic tests give a fuller picture of how a clot forms and breaks down, making them better suited for emergencies like major surgery, trauma, or liver failure. However, both types of tests serve distinct purposes, and the best approach for many patients is to use them together rather than treating them as competing options.

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Blood from patients infected with the Omicron COVID-19 variants clotted more than healthy controls but significantly less than blood from patients with Beta or Delta variants. Patients with the more severe variants also had more microscopic fibrin clots (microclots) in their plasma. This supports the idea that these microclots contribute to COVID-19 severity, and that measuring clotting abnormalities can serve as an objective marker of how dangerous a given variant is.

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This review examines three approaches to resuscitating severely bleeding trauma patients: fixed-ratio blood component therapy, whole blood transfusion, and goal-directed therapy guided by viscoelastic clot testing. Each strategy has different evidence bases, logistical demands, and theoretical foundations, and geographic variation in adoption reflects both resource availability and historical practice. The review argues for individualized, physiology-driven resuscitation using real-time clotting data as the most scientifically grounded approach.

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COVID-19 disrupts the fibrinolytic system at multiple points — from how the virus enters cells via the ACE2 receptor (linked to the same regulatory pathway as tPA and PAI-1) to the development of a dangerous hypercoagulable state in the lungs, kidneys, and other organs. This review traces the molecular connections between SARS-CoV-2 infection and fibrinolysis dysregulation and identifies several potential drug targets along those pathways. Understanding fibrinolysis is key to developing effective treatments for severe COVID-19.

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Three COVID-19 patients developed unusual and life-threatening coagulopathies — including a pulmonary embolus despite a supratherapeutic INR, unexpected fibrinolysis, and progressive thrombosis during severe hypocoagulability — that were navigated successfully using thromboelastography alongside aPTT. TEG revealed clotting dynamics that standard tests could not capture, enabling precise and individualized heparin management. The cases underscore that COVID-19 coagulopathy is heterogeneous and demands real-time, whole-blood monitoring.

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In 79 severely ill, anticoagulated COVID-19 patients, thromboelastography parameters combined with standard coagulation tests predicted both bleeding (with high accuracy) and thrombosis (with moderate accuracy). Using TEG guidance also reduced the need for red blood cell and plasma transfusions. Because COVID-19 patients can shift unpredictably between clotting and bleeding phenotypes, institutions need individualized, daily monitoring strategies rather than fixed anticoagulation protocols.

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Three critically ill COVID-19 patients with complex clotting disorders were successfully managed using thromboelastography (TEG) to guide anticoagulation, including cases where standard aPTT tests gave misleading results due to kidney failure, abnormal blood lipids, or polycythemia. TEG allowed clinicians to detect true hypercoagulability and adjust heparin dosing precisely, preventing both clots and bleeding. The cases demonstrate that standard tests alone are insufficient for COVID-19 patients with serious coagulopathy.

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Severe trauma kills primarily through massive hemorrhage and head injury early, and sepsis and organ failure later, with the fibrinolytic system playing a central role at every stage. The review covers how injury activates the endothelium, tissue factor, platelets, and the immune system, all of which feed back on fibrinolysis in complex ways. Insights from tranexamic acid trials and observations of wide variability in fibrinolytic activity after injury are reshaping how trauma-induced coagulopathy is understood and treated.

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Whole blood transfusion, long used in military trauma care, is increasingly being adopted in civilian urban trauma centers based on improved outcomes data and lessons from fixed-ratio component therapy trials. This commentary reviews the history, biological rationale, and logistical challenges of civilian whole blood programs. Ongoing randomized trials will determine whether whole blood provides a meaningful mortality benefit in civilian trauma compared to standard component therapy.

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COVID-19 patients lack pre-existing immunity to SARS-CoV-2, and most antiviral and anti-inflammatory therapies have shown limited effectiveness, making passive immunity an important treatment avenue. Convalescent plasma from recovered patients with high levels of neutralizing antibodies showed benefit in many COVID-19 cases, drawing on lessons from SARS and MERS. This review outlines the immune response to SARS-CoV-2 and evaluates the evidence for convalescent plasma while noting the ongoing challenge of developing durable vaccines.

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Fibrin, the protein scaffold of blood clots, promotes tumor growth by providing a surface for cancer cells to migrate and by delivering growth factors that stimulate new blood vessel formation. Components of the fibrinolytic system — including uPA, uPAR, and PAI-1 — further drive tumor invasion, cell signaling, and resistance to cell death through interactions with receptors and the extracellular matrix. While blocking these pathways suppresses tumors in animal models, human clinical trials are still needed to translate these findings into treatments.

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Acute promyelocytic leukemia (APL) carries a serious risk of early death from bleeding, driven by abnormal activation of both clotting and fibrinolysis that is distinct from typical disseminated intravascular coagulation. The leukemic cells overproduce tissue plasminogen activator (tPA) and its receptor annexin A2, creating excessive clot breakdown, with intracranial hemorrhage as the most deadly consequence. Despite effective cancer treatments, the early mortality rate from bleeding remains stubbornly high, underscoring the need for better understanding of the specific hemostatic abnormalities in APL.

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When devices made of non-biological materials such as artificial heart valves, stents, or dialysis catheters are placed inside blood vessels, blood contacts the foreign surface and triggers clotting, hemolysis, platelet loss, and infection. The type and severity of complications vary by device but share a common root cause: the absence of a natural endothelial lining on the device surface. Preventing these complications will require research focused on promoting re-endothelialization — the regrowth of the body's own vessel lining over implanted surfaces.

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A patient with newly diagnosed B-cell leukemia suffered a rapidly fatal hemolytic transfusion reaction caused by an IgM antibody against the red blood cell antigen 'c', an unusual and previously undescribed scenario. Unlike the more common slow IgG-mediated reactions, this IgM-driven hemolysis was immediate and overwhelming. Early recognition of this rare type of reaction is essential because prompt intervention may be the only chance to save the patient.

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Microparticles — tiny membrane fragments shed by cells when activated or dying — carry fibrinolytic proteins on their surface and can generate plasmin, the enzyme that dissolves clots. Different cell types produce microparticles with different fibrinolytic activities, making the overall effect on clotting complex and context-dependent. In cancer, microparticle-driven fibrinolysis may play a role in tumor spread, adding another layer to how the clotting system interacts with malignancy.

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Air can enter the veins when central catheters are placed or removed, especially if patient positioning allows an air-to-blood pressure gradient, and these air emboli can travel to the lungs, cross into the arteries, or ascend to the brain's venous system. The review updates the pathophysiology of venous air embolism and emphasizes that many cases are caused by preventable procedural errors. Healthcare workers performing catheter procedures need better awareness of positioning precautions to eliminate this avoidable complication.

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The newer direct oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, and apixaban offer more predictable drug levels and fewer food and drug interactions than warfarin, with notably lower rates of intracranial bleeding. However, questions about monitoring, dosing in special populations, and reversal strategies have emerged with wider use. This review synthesizes the evidence on NOAC efficacy, bleeding risks, and the evolving approaches to reversing their effects when needed.

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This study tracked tiny cell fragments called microparticles in the blood of pregnant women before and after delivery, looking at whether they might contribute to the increased clotting activity of pregnancy. Pregnancy itself was not associated with changes in microparticle numbers or their expression of tissue factor, a key clotting trigger. However, the act of giving birth increased the proportion of platelet-derived microparticles in women who had been in labor, suggesting delivery — rather than pregnancy itself — drives this shift.

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A retrospective review of 246 patients with blood clots in the portal, mesenteric, or hepatic veins found that liver disease, abdominal cancer, surgery, pancreatitis, and hereditary clotting disorders were the most common risk factors. Only 20% of portal vein thrombosis patients tested positive for the JAK2 mutation (lower than in published literature), and recurrence was common regardless of anticoagulation. The findings highlight the diverse causes of splanchnic vein thrombosis and the need for tailored anticoagulation strategies.

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Components of the plasminogen-plasmin system — particularly uPA, its receptor uPAR, and the inhibitor PAI-1 — promote tumor growth, invasion, spread, and new blood vessel formation in many types of cancer. Measuring levels of uPA, uPAR, and PAI-1 in tumor tissue provides strong prognostic information across cancers of the breast, colon, lung, and other organs. In breast cancer, these biomarkers are already being incorporated into clinical risk assessment to guide treatment decisions.

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The discovery that plasmin dissolves fibrin has grown into a vast field revealing that the plasminogen-plasmin system regulates embryo development, wound healing, cell movement, and the pathogenesis of atherosclerosis, cancer, neurodegeneration, and autoimmune disease. This historical review traces the key milestones in fibrinolysis research and connects them to current clinical applications including thrombolytic drugs and emerging small-molecule therapies targeting the system. The author reflects on personal observations spanning decades of work in this field.

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Desmopressin, a drug that releases von Willebrand factor and improves platelet stickiness, was given to 14 patients with intracerebral hemorrhage who had impaired platelet function. One hour after infusion, platelet function and von Willebrand factor levels improved significantly, and hematoma growth was modest in the half of patients treated within 12 hours. The drug was well tolerated, supporting the case for a larger trial to determine whether desmopressin can meaningfully limit bleeding in brain hemorrhage patients with platelet dysfunction.

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Older patients with low platelet counts face a higher bleeding risk than younger people, compounded by age-related changes in platelet function, more complex medication regimens, and greater overall illness burden. The review covers the major causes of thrombocytopenia in older adults, including immune-mediated forms and drug-induced cases. Clinicians managing older patients need to account for these age-specific factors when assessing bleeding risk and choosing treatment.