Congenital Thrombotic Thrombocytopenic Purpura (cTTP) can be rapidly diagnosed with this test. Severe deficiency of ADAMTS13 activity, negative for an inhibitor, represent putative cases of Upshaw-Schulman syndrome; this autosomal recessive inherited form of TTP can be confirmed by gene sequencing.

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.

Genetics can help confirm a diagnosis of Alport syndrome and may be especially helpful when the clinical phenotype is not clear-cut. Genetics can also inform family planning (for example, does an affected male have X-linked or autosomal Alport and is an affected female heterozygous or homozygous?).

SERPINC1 is the gene encoding antithrombin III (AT3) protein. AT3 deficiency is a common cause of inherited thrombophilia and may be as prevalent as 1:2000. Sequencing may help confirm the diagnosis.

Genetics can help confirm a C3G diagnosis which can be challenging due to technical issues with immunofluorescence. Furthermore, since there is no disease-specific treatment for C3G, genetics may help treatment decisions; for example, patients with mutations may respond more poorly to mycophenolate mofetil than those with nephritic factors.

Due to the homologous nature of these tandem genes, this complement-regulatory region is more susceptible to deletions and duplications. For example, rare deletions in this region that result in a fusion of the CFH gene to CFHR1 can cause atypical hemolytic uremic syndrome (aHUS). Other more common deletions of either CFHR3-1 or CFHR1-4 can be inherited such that many people are homozygous null for CFHR1; these people are more likely than others to develop anti-CFH antibodies, which can cause aHUS.

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.

This test can rapidly diagnose active infection from patients who are symptomatic, presymptomatic, or asymptomatic, facilitating proper quarantine, contact tracing, hospitalization, and treatment. A major obstacle in controlling the (COVID-19) pandemic is that patients are contagious while presymptomatic or asymptomatic.

Mutations in FGA, FGB, or FGG can cause dysfibrinogenemia or afibrinogenemia. Depending on the effect of the mutation, there may be a bleeding, thrombotic, or asymptomatic phenotype. This test may help confirm the diagnosis.

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.

Hemophilia B is due to mutations in the Factor IX (9) gene. Knowing the mutation can inform likelihood of inhibitor development, bleeding severity, family planning, and pregnancy and neonatal management. Over 10% of severe hemophilia B cases are due to large deletion or duplication variants which are very difficult to detect via sequencing.

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.

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.

The Factor V Leiden mutation causes resistance to activated protein C and is the most common inherited predisposition to venous thrombosis in Caucasian populations (40 to 50 percent of cases). Heterozygosity for the Factor V Leiden mutation confers an approximately sevenfold increased risk of thrombosis, while homozygosity for the mutation increases thrombosis risk 80-fold. It is present in 60% of thrombotic patients with normal levels of protein S, protein C, antithrombin, and antiphospholipid antibodies. The Factor V Leiden mutation has also been associated with spontaneous abortion and may be linked to recurrent pregnancy loss.

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.

Hemophilia A is due to mutations in the F8 gene. Knowing the mutation can inform likelihood of inhibitor development, bleeding severity, family planning, and pregnancy and neonatal management. Over 5% of severe hemophilia A cases are due to large deletion or duplication variants which are very difficult to detect via sequencing.

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.

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.

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.

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.