The condition is diagnosed by blood tests in the laboratory when it is noted that special blood clotting test are abnormal. Specifically prothrombin time (PT) or activated partial thromboplastin time(aPTT) are prolonged. The diagnosis is confirmed by an assay detecting very low or absent FXII levels.

The FXII (F12) gene is found on chromosome 5q33-qter.

In hereditary angioedema type III an increased activity of factor XII has been described.

The differential diagnosis for this inherited condition is the following: hemophilia A, factor XI deficiency, von Willebrand disease, fibrinogen disorders and Bernard-Soulier syndrome

Blood tests are neede to differentiate FVII deficiency from other bleeding disorders. Typical is a discordance between the prolonged prothrombin time (PT) and normal levels for the activated partial thromboplastin time (APTT). FVII levels are <10IU/dl in homozygous individuals, and between 20-60 in heterozygous carriers. The FCVII: C assay supports the diagnosis.

The FVII gene (F7) is found on chromosome 13q34. Heterogeneous mutations have been described in FVII deficient patients.

Two of the most common differential diagnoses are haemophilia B which is a deficiency in Factor IX and von Willebrand Disease which is a deficiency in von Willebrand factor (needed for the proper functioning of Factor VIII), haemophilia C is also a possible, differential diagnosis.

The diagnosis for hemophilia B can be done via the following tests/methods:

- Coagulation screening test

- Bleeding scores

- Coagulation factor assays

The diagnosis of hemophilia A may be suspected as coagulation testing reveals an increased PTT in the context of a normal PT and bleeding time. PTT tests are the first blood test done when haemophilia is indicated. However, the diagnosis is made in the presence of very low levels of Factor VIII. A family history is frequently present, although not essential. Recently, genetic testing has been made available to determine an individual's risk of attaining or passing on hemophilia. Diagnosis of haemophilia A also includes a severity level which can range from mild to severe based on the amount of active and functioning factor VIII detected in the blood. Factor VIII levels do not typically change throughout an individual's life. Severe haemophilia A is the most common form occurring in the majority of affected people. Individuals with mild haemophilia often experience few or no bleeding episodes except in the case of serious trauma (i.e. tooth extraction, or surgery).

When vWD is suspected, blood plasma of a patient must be investigated for quantitative and qualitative deficiencies of vWF. This is achieved by measuring the amount of vWF in a vWF antigen assay and the functionality of vWF with a glycoprotein (GP)Ib binding assay, a collagen binding assay, or a ristocetin cofactor activity (RiCof) or ristocetin induced platelet agglutination (RIPA) assays. Factor VIII levels are also performed because factor VIII is bound to vWF which protects the factor VIII from rapid breakdown within the blood. Deficiency of vWF can then lead to a reduction in factor VIII levels, which explains the elevation in PTT. Normal levels do not exclude all forms of vWD, particularly type 2, which may only be revealed by investigating platelet interaction with subendothelium under flow, a highly specialized coagulation study not routinely performed in most medical laboratories. A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the other agonists used. A platelet function assay may give an abnormal collagen/epinephrine closure time, and in most cases, a normal collagen/ADP time. Type 2N may be considered if factor VIII levels are disproportionately low, but confirmation requires a "factor VIII binding" assay. Additional laboratory tests that help classify sub-types of vWD include von-willebrand multimer analysis, modified ristocetin induced platelet aggregation assay and vWF propeptide to vWF antigen ratio propeptide. In cases of suspected acquired von-Willebrand syndrome, a mixing study study (analysis of patient plasma along with pooled normal plasma/PNP and a mixture of the two tested immediately, at one hour, and at two hours) should be performed. Detection of vWD is complicated by vWF being an acute phase reactant with levels rising in infection, pregnancy, and stress.

Other tests performed in any patient with bleeding problems are a complete blood count-CBC (especially platelet counts), activated partial thromboplastin time-APTT, prothrombin time with International Normalized Ratio-PTINR, thrombin time-TT, and fibrinogen level. Testing for factor IX may also be performed if hemophilia B is suspected. Other coagulation factor assays may be performed depending on the results of a coagulation screen. Patients with von Willebrand disease typically display a normal prothrombin time and a variable prolongation of partial thromboplastin time.

The testing for vWD can be influenced by laboratory procedures. Numerous variables exist in the testing procedure that may affect the validity of the test results and may result in a missed or erroneous diagnosis. The chance of procedural errors are typically greatest during the preanalytical phase (during collecting storage and transportation of the specimen) especially when the testing is contracted to an outside facility and the specimen is frozen and transported long distances. Diagnostic errors are not uncommon, and the rate of testing proficiency varies amongst laboratories, with error rates ranging from 7 to 22% in some studies to as high as 60% in cases of misclassification of vWD subtype. To increase the probability of a proper diagnosis, testing should be done at a facility with immediate on-site processing in a specialized coagulation laboratory.

A pregnant woman with a history of haemophilia in her family can test for the haemophilia gene. Such tests include:

- chorionic villus sampling (CVS) – a small sample of the placenta is removed from the womb and tested for the haemophilia gene, usually during weeks 11-14 of pregnancy

- amniocentesis – a sample of amniotic fluid is taken for testing, usually during weeks 15-20 of pregnancy

There's a small risk of these procedures causing problems such as miscarriage or premature labour, so the woman may discuss this with the doctor in charge of her care.

Genetic testing and counselling are available to help determine the risk of passing the condition onto a child. This may involve testing a sample of tissue or blood to look for signs of the genetic mutation that causes haemophilia.

In congenital FXII deficiency treatment is not necessary. In acquired FXII deficiency the underlying problem needs to be addressed.

The diagnosis of this condition can be done via the following:

- Flow cytometry

- Bleeding time analysis

The diagnosis for deficiency of protein S can be done via reviewing family history of condition and genetic testing, as well as the following:

- Protein S antigen test

- Coagulation test (prothrombin time test)

- Thrombotic disease investigation

- Factor V Leiden test

There are several treatments available for factor VII deficiency; they all replace deficient FVII.

1. Recombinant FVIIa concentrate (rFVIIa) is a recombinant treatment that is highly effective and has no risk of fluid overload or viral disease. It may be the optimal therapy.

2. Plasma derived Factor VII concentrate (pdFVII) : This treatment is suitable for surgery but can lead to thrombosis. It is virus attenuated.

3. Prothrombin complex concentrate (PCC) containing factor VII: this treatment is suitable for surgery, but has a risk of thrombosis. It is virus attenuated.

4. Fresh frozen plasma (FFP): This is relatively inexpensive and readily available. While effective this treatment carries a risk of blood-borne viruses and fluid overload.

Diagnosis of inherited hypoprothrombinemia, relies heavily on a patient's medical history, family history of bleeding issues, and lab exams performed by a hematologist. A physical examination by a general physician should also be performed in order to determine whether the condition is congenital or acquired, as well as ruling out other possible conditions with similar symptoms. For acquired forms, information must be taken regarding current diseases and medications taken by the patient, if applicable.

Lab tests that are performed to determine diagnosis:

1. Factor Assays: To observe the performance of specific factors (II) to identify missing/poorly performing factors. These lab tests are typically performed first in order to determine the status of the factor.

2. Prothrombin Blood Test: Determines if patient has deficient or low levels of Factor II.

3. Vitamin K1 Test: Performed to evaluate bleeding of unknown causes, nosebleeds, and identified bruising. To accomplish this, a band is wrapped around the patient's arm, 4 inches above the superficial vein site in the elbow pit. The vein is penetrated with the needle and amount of blood required for testing is obtained. Decreased vitamin K levels are suggestive of hypoprothrombinemia. However, this exam is rarely used as a Prothrombin Blood Test is performed beforehand.

The diagnosis of haemophilia C (factor XI deficiency) is centered on prolonged activated partial thromboplastin time.One will find that the factor XI has decreased in the individuals body.In terms of differential diagnosis one must consider:factor VIII deficiency, lupus anticoagulant and heparin contamination.

Among the possibilities for differential diagnosis of protein S deficiency are- Antiphospholipid syndrome, disseminated intravascular coagulation and antithrombin deficiency (though this list is not exhaustive)

In terms of hemophilia C medication cyklokapron is often used for both treatment after an incident of bleeding and as a preventative measure to avoid excessive bleeding during oral surgery.

Treatment is usually not necessary, except in relation to operations, leading to many of those having the condition not being aware of it. In these cases, fresh frozen plasma or recombinant factor XI may be used, but only if necessary.

The afflicted may often suffer nosebleeds, while females can experience unusual menstrual bleeding which can be avoided by taking birth control such as: IUDs and oral or injected contraceptives to increase coagulation ability by adjusting hormones to levels similar to pregnancy.

A 28 month old girl, showed symptoms from 8 months of age and consisted of complaints of painful bruises over lower limbs, and disturbed, painful sleep at night. Family history revealed older brother also suffered similar problems and died at age of two years possibly due to bleeding - no diagnosis was confirmed. Complete blood count and blood smear was determined as normal. No abnormality in fibrinogen, liver function test, and bleeding time. However, prothrombin levels were less than 1% so patient was transfused with fresh frozen plasma (FFP). Post transfusion methods, patient is now 28 months old and living healthy life. The only treatment that is needed to date is for the painful bruises, which the patient is given FFP every 5-6 weeks.

Twelve day old boy admitted for symptoms consisting of blood stained vomiting and dark colored stool. Upon admission into hospital, patient received vitamin K and FFP transfusion. No family history of similarity in symptoms that were presented. At 40 days old, patient showed symptoms of tonic posturing and constant vomiting. CT scan revealed subdural hemorrhage, and other testing showed low hb levels of 7%, platelets at 3.5 lakhs/cu mm. PT examination was 51 seconds and aPTT at 87 seconds. Prothrombin activity levels were less than 1%. All other exams revealed no abnormalities. Treatment methods included vitamin K and FFP, as well as ventilator support and packed red blood cell transfusion (PRBC). At half a year of age, condition consisted of possible poor neurological outcome secondary to CNS bleeding. Treatment of very frequent transfusion was needed for patient.

Recent study illustrated a patient with 2 weeks of continuous bleeding, with presence of epistaxis, melena, hematuria, and pruritic rash with no previous bleeding history. Vitals were all within normal range, however, presence of ecchymoses was visible in chest, back and upper areas. Lab exams revealed prolonged prothrombin time (PT) of 34.4 and acquired partial thromboplastin time (aPTT) of 81.7, as well as elevated liver function tests. Discontinuation of atorvastatin, caused liver enzymes to go back to normal. Treatment of vitamin K, antibiotics, and fresh frozen plasma (FFP) did not have an impact on coagulopathy. Mixing of PT and aPTT was performed in order to further evaluate coagulopathy and revealed no correction. Factor activity assays were performed to determine the presence of a specific one. Testing revealed that factor II activity could not be quantified. Further studies showed that acquired factor II inhibitor was present without the lupus anticoagulant, with no clear cause associated with the condition. Aimed to control bleeding and getting rid of the inhibitor through directly treating the underlying disease or through immunosuppressive therapy. Corticosteroids and intravenous immunoglobulin improved the PT and aPTT. Did not improve bleeding conditions until treatment of transfusion with activated PCC. Treatment of inhibitor required Rituximab, which was shown to increase factor II levels to 264%. Study shows that when a patient with no history of coagulopathy presents themselves with hemorrhagic diathesis, direct testing of a factor II inhibitor should be performed initially.

There are two main types of protein C assays, activity and antigen (immunoassays). Commercially available activity assays are based on chromogenic assays that use activation by snake venom in an activating reagent, or clotting and enzyme-linked immunosorbant assays. Repeated testing for protein C functional activity allows differentiation between transient and congenital deficiency of protein C.

Initially, a protein C activity (functional) assay can be performed, and if the result is low, a protein C antigen assay can be considered to determine the deficiency subtype (Type I or Type II). In type I deficiencies, normally functioning protein C molecules are made in reduced quantity. In type II deficiencies normal amounts of dysfunctional protein C are synthesized.

Antigen assays are immunoassays designed to measure the quantity of protein C regardless of its function. Type I deficiencies are therefore characterized by a decrease in both activity and antigen protein C assays whereas type II deficiencies exhibit normal protein C antigen levels with decreased activity levels.

The human protein C gene (PROC) comprises 9 exons, and protein C deficiency has been linked to over 160 mutations to date. Therefore, DNA testing for protein C deficiency is generally not available outside of specialized research laboratories.

Manifestation of purpura fulminans as it is usually associated with reduced protein C plasma concentrations of <5 mg IU/dL. The normal concentration of plasma protein C is 70 nM (4 µg/mL) with a half live of approximately 8 hours. Healthy term neonates, however, have lower (and more variable) physiological levels of protein C (ranging between 15-55 IU/dL) than older children or adults, and these concentrations progressively increase throughout the first 6 months of life. Protein C levels may be <10 IU/dL in preterm or twin neonates or those with respiratory distress without manifesting either purpura fulminans or disseminated intravascular coagulation.

The prevalence of vWD is about one in 100 individuals. However, the majority of these people do not have symptoms. The prevalence of clinically significant cases is one per 10,000. Because most forms are rather mild, they are detected more often in women, whose bleeding tendency shows during menstruation. It may be more severe or apparent in people with blood type O.

Fresh frozen plasma and cryoprecipitate are the mainstay of therapy for Factor XIII deficiency, but carry risk related to transfusion.

There are several treatments available for bleeding due to factor X deficiency, however a specifi FX concentrate is not available (2009).

1. Prothrombin complex concentrate (PCC) supplies FX with a risk of thrombosis.

2. Fresh frozen plasma (FFP): This is relatively inexpensive and readily available. While effective this treatment carries a risk of blood-borne viruses and fluid overload.

3. If vitamin K levels are low, vitamin K can be supplied orally or parenterally.

Treatment of FX deficiency in amyloidosis may be more complex and involve surgery (splenectomy) and chemotherapy.

Blood tests are needed to differentiate FX deficiency from other bleeding disorders. Typical are normal thrombin time, prolonged prothrombin time (PT) and prolonged partial thromboplastin time(PTT). FX antigen and its coagulant activity can be used to classify the severity of the condition:

1. Type I has low levels of FX antigen and activity.

2. Type II has low coagulant activity but normal or borderline FX antigen levels.

The FX (F10) gene is found on chromosome 13q34. Heterogeneous mutations have been described in FX deficient patients.

Two commercially produced factor XIII concentrates are currently available in Europe, one manufactured by Bio Products Laboratory (BPL) and only available in the United Kingdom. The other, Fibrogammin-P, is produced by Beringwerke of Germany. In the U.S. FXIII concentrate is only available under the Federal Drug Administration's Investigational New Drug (IND) Program, or through clinical trial.

Platelet storage pool deficiency has no treatment however management consists of antifibrinolytic medications if the individual has unusual bleeding event, additionally caution should be taken with usage of NSAIDS