Machaon provides the fastest ADAMTS13 activity and inhibitor testing available in the US. Rapid diagnosis and administration of correct treatment is paramount for TTP and aHUS. This test is diagnostic for Thrombotic Thrombocytopenic Purpura (TTP) when ADAMTS13 Activity levels are below 10%. Consider other Thrombotic Microangiopathies (TMAs), such as atypical Hemolytic Uremic Syndrome (aHUS), for ADAMTS13 Activity levels above 10%.

The clinical presentation of thrombotic microangiopathy (TMA) has been associated with multiple genetic disease including atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), C3 glomerulopathy (C3G, comprising dense deposit disease and C3 glomerulonephritis), congenital B12 deficiency and others. These are difficult-to-diagnose, very sick patients with distinct treatment depending on the nature of the TMA. Accurate, rapid diagnosis is critical. Additionally, patients with the C5 p.Arg885 polymorphism may respond poorly to the current approved therapy, eculizumab. Note: this is the third time (3.0 name designation) we have updated the gene list to reflect the most current understanding of aHUS/TMA in the scientific literature.

This panel will detect laboratory abnormalities characteristic of Antiphospholipid Syndrome (APS), including the presence of a lupus anticoagulant, antibodies against the membrane phospholipid cardiolipin (IgG, IgM and IgA isotypes) and antibodies against B2GP1 (IgG, IgM and IgA isotypes). Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening form of APS characterized by the presence of a triple-positive APS lab work-up. Detecting a single, double, or triple positive result can significantly change patient management. Lupus anticoagulant and antiphospholipid antibodies increase the risk of arterial thrombosis, venous thrombosis, thrombocytopenia and recurrent miscarriage.

The CoagGenex Clotting Genetic Panel is an amplicon-based, next-generation DNA sequencing assay targeting the exons of 28 relevant genes [protein S (PROS1), protein C (PROC), antithrombin III (SERPINC1), factor VIII (F8), factor V (F5), factor II (F2), fibrinogen (FGA), plasminogen (PLG), plasminogen activator inhibitor, type I (formerly called PAI1, now SERPINE1), ADAMTS13, CBS, FGB, FGG, F11, F12, F13A, F13B, F7, F9, HRG, MAST2, PLAT, PROCR, SERPIND1, STAB2, TFPI, THBD, and VWF)]. This panel also detects the CYP2C9 (*2, *3, *5, *6, *8, *11), CYP2C cluster rs12777823, and VKORC1 (*2) variants affecting warfarin sensitivity, which is an anticoagulant frequently used to treat or prevent venous thromboembolism (VTE). Genetic testing may be helpful for confirming diagnosis, estimating risk of recurrence and asymptomatic diagnosis in affected families.

HLH is a life-threatening condition requiring rapid diagnosis and treatment. CXCL9 can differentiate HLH from sepsis and persistent systemic inflammatory response syndrome (SIRS). CXCL9 levels quickly and significantly decreased with emapalumab treatment in HLH patients and low levels of CXCL9 were associated with treatment response. Emapalumab neutralizes IFNγ activity; CXCL9 is a marker for IFNγ activity.

Diagnosing Cytokine Release Syndrome (CRS) immediately is vital. CRS can rapidly escalate into a life-threatening condition. CRS results from an excessive immune response, often triggered by immunotherapies like chimeric antigen receptor T cell therapy (CAR-T), bone marrow transplant or infections, leading to a massive release of pro-inflammatory cytokines. The degree of elevation often correlates with the severity of the clinical syndrome. For example, large elevations in IL-6 support the diagnosis of CRS. Design note: the tests included in this panel are based on the current (2024) recommendations from 25 physician key opinion leaders (KOLs) from major academic medical centers from across the US, including: CHOP, UCSF (2), Stanford, Children's Alabama (2), Kaiser SF, Valley Children's, CHOC (3), Phoenix Children's, Cook Children's, UC Davis, Stanford Children's, University of Michigan Health, Johns Hopkins, Hershey, St. Jude, NIH, St. Louis Children's, Loma Linda Children's, UCSD, and UC Davis.

The type of mutation correlates with disease severity and likelihood of inhibitor formation. Mutation detection can confirm the diagnosis when the traditional lab workup is muddied by complicating factors like inflammation, stress, infection, hormone replacement therapy, age, acute phase response, menstrual cycle, pregnancy, exercise, ABO blood type, or lupus anticoagulant. Confirming carrier status can inform family planning decisions.

Acquired factor deficiencies may occur due to the development of factor-specific inhibitory antibodies. These antibodies may also develop against factor replacement products in patients with a congenital deficiency. This test may be used to detect and quantitate inhibitory antibodies against Factor VIII. This assay is suitable for the detection of Factor VIII inhibitors in patients on the recombinant, monoclonal antibody treatment Hemlibra (emicizumab).

Up to 5 percent of patients receiving heparin develop heparin-induced thrombocytopenia (HIT), a life-threatening complication that can occur following exposure to heparin, regardless of the dose, schedule, or route of administration. The mortality rate can be as high as 20 percent; with early diagnosis, mortality rates have been reported as low as 2 percent. Ruling out HIT quickly can achieve both significant cost savings and experience better patient outcomes. This is a highly sensitive screening test for clinical HIT, allowing rapid rule out with a negative result. Positive results should be confirmed with a functional assay to assess the ability of antibodies to activate platelets.

This extended panel adds 9 additional genes to the HLH Genetic Panel 3.0, making it the most comprehensive approach to characterize HLH patients. The additional 9 genes are more rarely associated with HLH so they have been separated out into this extended panel option. Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening disease where an underlying immune defect and/or triggering event initiates excessive activation of immune cells (macrophages and lymphocytes) leading to multi-organ dysfunction and failure. Treatment of HLH may vary depending on the underlying cause, including whether a genetic cause is detected. Timely diagnosis has been a major challenge, with patients having to start aggressive therapies or be admitted to the ICU before final diagnostic results are available. Note: this is the third time (3.0 name designation) we have updated the gene list to reflect the most current understanding of HLH in the scientific literature.

Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening disease where an underlying immune defect and/or triggering event initiates excessive activation of immune cells (macrophages and lymphocytes) leading to multi-organ dysfunction and failure. Treatment of HLH may vary depending on the underlying cause, including whether a genetic cause is detected. Timely diagnosis has been a major challenge, with patients having to start aggressive therapies or be admitted to the ICU before final diagnostic results are available. Note: this is the third time (3.0 name designation) we have updated the gene list to reflect the most current understanding of HLH in the scientific literature.

This panel was designed as an initial work-up to detect the most common causes of thrombophilia in patients suspected of being at risk for thrombosis.

IL-18 is a marker of monocyte-related inflammation and is commonly used to characterize hyperinflammation syndromes, where elevations are associated with HLH, MAS and other hyperinflammatory syndromes. This test can measure levels of IL-18 up to 117,120pg/mL. Ordering the extended version of this test (see standard order form) is required to detect levels above 117,120pg/mL.

Complement-mediated diseases such as atypical hemolytic uremic syndrome (aHUS) and catastrophic antiphospholipid syndrome (CAPS) are difficult to diagnose. Accurate and rapid diagnosis is critical. The bioluminescent modified Ham (mHam) cell-based functional complement assay detects abnormal complement deposition using cell viability as the readout. Complement-mediated cell death in the mHam assay uses a human kidney cell line modified by genetic deletion of complement regulator CD46 and is blocked by addition of complement inhibitors. Positive mHam results will reflex to addition of C5 inhibitor to assess whether complement-mediated cell killing is blocked in vitro. Soluble C5b-9 levels are measured as part of this assay. This assay may help to diagnose and treat complement-mediated diseases. The '2.0' in the test name represents recent improvements in this assay (Cole, M. et al. Blood. 2024) from when the assay was first introduced (Gavriilaki E, et al. Blood. 2015). https://mham.machaondiagnostics.com/

Plasminogen is a single chain glycoprotein zymogen and is the precursor of the fibrinolytic enzyme plasmin. Plasminogen deficiencies are classified as hypoplasminogenemia (type I) or dysplasminogenemia (type 2) and are associated with decreased extracellular fibrin clearance leading to mucous membrane lesions and ligneous conjunctivitis.

Comprehensive platelet aggregation studies should be included as part of initial bleeding workups to detect defects in platelet function. Platelets promote hemostasis by four interconnected mechanisms: 1) Adhering to sites of vascular injury or artificial surfaces, 2) Releasing compounds from their granules, 3) Aggregating together to form a hemostatic platelet plug and 4) Providing a procoagulant surface for activated coagulation protein complexes on their phospholipid membranes [2]. Since the activation of platelets is a multiphasic reaction involving different membrane bound receptors and intracellular signaling pathways, using multiple agonists at different concentrations is necessary to adequately assess platelet function and characterize abnormalities. This test can detect platelet function abnormalities associated with Glanzmann thrombasthenia, Bernard Soulier, von Willebrand Disease, ADP receptor defects, dense granule deficiency, and use of antiplatelet medications such as aspirin or Plavix.

Platelet functional defects have been linked to more than 23% of patients with bleeding of unknown cause, highlighting the need to clinically differentiate platelet, fibrinogen and von Willebrand abnormalities. This panel can confirm the diagnosis of more common platelet aggregation, platelet secretion (ATP release) and platelet signaling defects; it can also diagnose (and subtype) von Willebrand disease, dysfibrinogenemias and rare platelet defects (Glanzmann thrombasthenia, Bernard-Soulier, Wiskott-Aldrich, Hermansky-Pudlak, Scott, MayHegglin syndromes, others).

Thrombocytopenia can range from severe to mild or asymptomatic. Thrombocytopenia can be acquired or inherited and genetic results can help differentiate between the two. The clinical significance of bleeding symptoms is difficult to assess, as concurrent bleeding disorders are commonly seen in the same patient. Gene sequencing of the thrombocytopenia-associated and von Willebrand factor genes can provide valuable understanding of the pathophysiology of bleeding diathesis.

To evaluate prolongations in the aPTT, Machaon utilizes three (3) different aPTT reagents: standard, lupus anticoagulant sensitive and factor sensitive (aPTT, aPTT-LA and aPTT-FS, respectively). A single aPTT reagent does not provide the range of sensitivities sufficiently suitable to characterize the various samples encountered in the clinical setting, including but not limited to anticoagulant monitoring, factor deficiency detection and lupus anticoagulant screening.

The PROC gene encodes protein C, a critical component of the anticoagulation system. PROC mutations can cause inherited thrombophilia.