Treatment of asymptomatic congenital dysfibrinogenemia depends in part on the expectations of developing bleeding and/or thrombotic complications as estimated based on the history of family members with the disorder and, where available, determination of the exact mutation causing the disorder plus the propensity of the particular mutation type to develop these complications. In general, individuals with this disorder require regular follow-up and multidiscipline management prior to surgery, pregnancy, and giving childbirth. Women with the disorder appear to have an increased rate of miscarriages and all individuals with fibrinogen activity in clotting tests below 0.5 grams/liter are prone to bleeding and spontaneous abortions. Women with multiple miscarriages and individuals with excessively low fibrinogen activity levels should be considered for prophylaxis therapy with fibrinogen replacement during pregnancy, delivery, and/or surgery.

In a study of 189 individuals diagnosed with congenital dysfibrinogenemia, ~33% were asymptomatic, ~47% experienced episodic bleeding, and ~20% experienced episodic thromboses. Due to the rareness of this disorder, treatment of individuals with these presentations are based primarily on case reports, guidelines set by the United Kingdom, and expert opinions rather than controlled clinical studies.

Critics of the diagnosis complain that case evidence is spotty and lacking controlled clinical studies.

Aside from observing the symptoms characteristic of X-linked thrombocytopenia in infancy (easy bruising, mild anemia, mucosal bleeding), molecular genetic testing would be done to confirm the diagnosis. Furthermore, flow cytometry or western blotting would be used to test for decreased or absent amounts of WASp. Family history would also assist in diagnosis, with specific attention to maternally related males with "WAS"-related disorders. Because "WAS"-related disorders are phenotypically similar, it is important to confirm the absence of the diagnostic criteria for Wiskoff-Aldrich syndrome at the outset. These diagnostic criteria include eczema, lymphoma, autoimmune disorder, recurrent bacterial or viral infections, family history of maternally related males with a "WAS"-related disorder, and absent or decreased "WASp". X-linked congenital neutropenia can be diagnostically distinguished from XLT with persistent neutropenia, arrested development of the bone marrow, and normal "WASp" expression.

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

- Flow cytometry

- Bleeding time analysis

People may be diagnosed after prolonged and/or recurring bleeding episodes. Children and adults may also be diagnosed after profuse bleeding after a trauma or tooth extraction. Ultimately, a laboratory diagnosis is usually required. This would utilize platelet aggregation studies and flow cytometry.

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.

Hydroxycarbamide and anagrelide are contraindicated during pregnancy and nursing. Essential thrombocytosis can be linked with a three-fold increase in risk of miscarriage. Throughout pregnancy, close monitoring of the mother and fetus is recommended. Low-dose low molecular weight heparin (e.g. enoxaparin) may be used. For life-threatening complications, the platelet count can be reduced rapidly using platelet apheresis, a procedure that removes platelets from the blood and returns the remainder to the patient.

Those diagnosed are usually treated with taking a low dose (80–100 mg) Aspirin a day. Anticoagulants (e.g. Warfarin, Coumadin) or clopidogrel (Plavix) are often additionally prescribed following formation of a medically significant clot. Thrombelastography is more commonly being used to diagnose hypercoagulability and monitor anti-platelet therapy.

There has been no general recommendation for treatment of patients with Giant Platelet Disorders, as there are many different specific classifications to further categorize this disorder which each need differing treatments. Platelet transfusion is the main treatment for people presenting with bleeding symptoms. There have been experiments with DDAVP (1-deamino-8-arginine vasopressin) and splenectomy on people with Giant platelet disorders with mixed results, making this type of treatment contentious.

The diagnostic workup is directed by the presenting signs and symptoms, and can involve:

- blood counts, clotting studies, and other laboratory testing

- imaging tests (ultrasound, CT scan, MRI, sometimes angiography, and rarely nuclear medicine scans)

- biopsy of the tumor.

Patients uniformly show severe thrombocytopenia, low fibrinogen levels, high fibrin degradation products (due to fibrinolysis), and microangiopathic hemolysis.

Anti-platelet autoantibodies in a pregnant woman with ITP will attack the patient's own platelets and will also cross the placenta and react against fetal platelets. Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by ITP will have platelet counts <50,000/uL and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with neonatal alloimmune thrombocytopenia (NAIT).

No lab test can reliably predict if neonatal thrombocytopenia will occur. The risk of neonatal thrombocytopenia is increased with:

- Mothers with a history of splenectomy for ITP

- Mothers who had a previous infant affected with ITP

- Gestational (maternal) platelet count less than 100,000/uL

It is recommended that pregnant women with thrombocytopenia or a previous diagnosis of ITP should be tested for serum antiplatelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable antiplatelet antibody should be started on therapy for their ITP which may include steroids or IVIG. Fetal blood analysis to determine the platelet count is not generally performed as ITP-induced thrombocytopenia in the fetus is generally less severe than NAIT. Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia. It is recommended that neonates be followed with serial platelet counts for the first few days after birth.,

A diagnosis of TTP is based on the clinical symptoms with the concomitant presence of thrombocytopenia (platelet count below 100×10/L) and microangiopathic hemolytic anemia with schistocytes on the blood smear, a negative direct antiglobulin test (coombs test), elevated levels of hemolysis markers (such as total bilirubin, LDH, free hemoglobin and an unmeasurable haptoglobin), after exclusion of any other apparent cause.

USS can present similar to the following diseases which have to be excluded: fulminant infections, disseminated intravascular coagulation, autoimmune hemolytic anemia, Evans syndrome, the typical and atypical form of hemolytic uremic syndrome (HUS), HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, pre-eclampsia, heparin-induced thrombocytopenia (HIT), cancer that is often accompanied with metastasis, kidney injury, antiphospholipid antibody syndrome and side effects from hematopoietic stem cell transplantation.

Of note is that pregnancy associated affections like pre-eclampsia, eclampsia and HELLP syndrome can overlap in their presentation as pregnancy can trigger TTP episodes.

Patients with fulminant infections, disseminated intravascular coagulation, HELLP syndrome, pancreatitis, liver disease and other active inflammatory conditions may have reduced ADAMTS13 activity but almost never a relevant severe ADAMTS13 deficiency <10% of the normal.

A severe ADAMTS13 deficiency below 5% or <10% of the normal (depending on the definitions) is highly specific for the diagnosis of TTP. ADAMTS13 activity assays are based on the direct or indirect measurement of VWF-cleavage products. Its activity should be measured in blood samples taken before therapy has started, to prevent false high ADAMTS13 activity. If a severe ADAMTS13 deficiency is present an ADAMTS13 inhibitor assay is needed to distinguish between the acquired, autoantibody-mediated and the congenital form of TTP (USS). The presence of antibodies can be tested by ELISA or functional inhibitor assays. The level of ADAMTS13 inhibitor may be fluctuating over the course of disease and depends on free circulatory antibodies, therefore an onetime negative test result does not always exclude the presence of ADAMTS13 inhibitors and thereby an autoimmune origin of TTP. A severe ADAMTS13 deficiency in the absence of an inhibitor, confirmed on a second time point in a healthy episode of a possible USS patient, usually sets the trigger to perform a molecular analysis of the "ADAMTS13" gene to confirm a mutation. In unclear cases a plasma infusion trial can be done, showing an USS in the absence of anti-ADAMTS13-antibodies a full recovery of infused plasma-ADAMTS13 activity as well as a plasma half-life of infused ADAMTS13 activity of 2–4 days. A deficiency of ADAMTS13 activity in first-degree relatives is also a very strong indicator for an Upshaw-Schulman Syndrome.

The following revised diagnostic criteria for essential thrombocythaemia were proposed in 2005. The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6. The criteria are as follows:

- A1. Platelet count > 450 × 10/µL for at least 2 months.

- A2. Acquired V617F JAK2 mutation present

- B1. No cause for a reactive thrombocytosis

- normal inflammatory indices

- B2. No evidence of iron deficiency

- stainable iron in the bone marrow or normal red cell mean corpuscular volume

- B3. No evidence of polycythemia vera

- hematocrit < midpoint of normal range or normal red cell mass in presence of normal iron stores

- B4. No evidence of chronic myeloid leukemia

- But the Philadelphia chromosome may be present in up to 10% of cases. Patients with the Philadelphia chromosome have a potential for the development of acute leukemia, especially acute lymphocytic leukemia.

- B5. No evidence of myelofibrosis

- no collagen fibrosis and ≤ grade 2 reticulin fibrosis (using 0–4 scale)

- B6. No evidence of a myelodysplastic syndrome

- no significant dysplasia

- no cytogenetic abnormalities suggestive of myelodysplasia

The incidence of acute TTP in adults is around 1.7–4.5 per million and year. These cases are nearly all due to the autoimmune form of TTP, where autoantibodies inhibit ADAMTS13 activity. The prevalence of USS has not yet been determined but is assumed to constitute less than 5% of all acute TTP cases. The syndrome's inheritance is autosomal recessive, and is more often caused by compound heterozygous than homozygous mutations. The age of onset is variable and can be from neonatal age up to the 5th–6th decade. The risk of relapses differs between affected individuals. Minimization of the burden of disease can be reached by early diagnosis and initiation of prophylaxis if required.

The differential diagnosis for Bernard–Soulier syndrome includes both Glanzmann thrombasthenia and pediatric Von Willebrand disease. BSS platelets do not aggregate to ristocetin, and this defect is not corrected by the addition of normal plasma, distinguishing it from von Willebrand disease.

Maternal and paternal platelet antigen phenotyping and screening of the maternal serum for anti-platelet antibodies can be performed.

Additionally, platelet antigen genotyping can be performed on the maternal and paternal blood to determine the exact nature of the incompatibility.

Neonatal platelet counts on laboratory testing are typically under 20,000 μL. Higher counts may suggest a different diagnosis, such as maternal immune thrombocytopenic purpura.

The most rapidly effective treatment in infants with severe hemorrhage and/or severe thrombocytopenia (30,000 μL) an infusion of (1 g/kg/day for two days) in the infant has been shown to rapidly increase platelet count and reduce the risk of related injury.

After a first affected pregnancy, if a mother has plans for a subsequent pregnancy, then the mother and father should be typed for platelet antigens and the mother screened for alloantibodies. Testing is available through reference laboratories (such as ). testing of the father can be used to determine zygosiity of the involved antigen and therefore risk to future pregnancies (if homozygous for the antigen, all subsequent pregnancies will be affected, if heterozygous, there is an approximate 50% risk to each subsequent pregnancy). During subsequent pregnancies, the genotype of the fetus can also be determined using amniotic fluid analysis or maternal blood as early as 18 weeks gestation to definitively determine the risk to the fetus.

In many cases, MHA requires no treatment. However, in extreme cases, blood platelet transfusions may be necessary

Laboratory tests might include: full blood count, liver enzymes, renal function and erythrocyte sedimentation rate.

If the cause for the high platelet count remains unclear, bone marrow biopsy is often undertaken, to differentiate whether the high platelet count is reactive or essential.

Recent studies have found that the life expectancy of males with XLT is not significantly affected. Individuals with XLT typically experience milder symptoms than those with other "WAS"-related disorders. For this reason, the long term prognosis for individuals with XLT is generally positive as long as symptoms are managed appropriately. Enhanced treatment methods in the past two decades have significantly improved the prognosis as well.

TTP is characterized by thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to microangiopathic hemolytic anemia and thrombocytopenia. This characteristic is shared by two related syndromes, hemolytic-uremic syndrome (HUS) and atypical hemolytic uremic syndrome (aHUS). Consequently, differential diagnosis of these TMA-causing diseases is essential. In addition to TMA, one or more of the following symptoms may be present in each of these diseases: neurological symptoms (e.g. confusion, cerebral convulsions seizures,); kidney impairment (e.g. elevated creatinine, decreased estimated glomerular filtration rate [eGFR], abnormal urinalysis); and gastrointestinal (GI) symptoms (e.g. diarrhea nausea/vomiting, abdominal pain, gastroenteritis. Unlike HUS and aHUS, TTP is known to be caused by an acquired defect in the ADAMTS13 protein, so a lab test showing ≤5% of normal ADAMTS13 levels is indicative of TTP. ADAMTS13 levels above 5%, coupled with a positive test for shiga-toxin/enterohemorrhagic "E. coli" (EHEC), are more likely indicative of HUS, whereas absence of shiga-toxin/EHEC can confirm a diagnosis of aHUS.

In terms of treatment/management, bleeding events can be controlled by platelet transfusion.

Most heterozygotes, with few exceptions, do not have a bleeding diathesis. BSS presents as a bleeding disorder due to the inability of platelets to bind and aggregate at sites of vascular endothelial injury. In the event of an individual with mucosal bleeding tranexamic acid can be given.

The affected individual may need to avoid contact sports and medications such as aspirin, which can increase the possibility of bleeding. A potential complication is the possibility of the individual producing antiplatelet antibodies

In adults, particularly those living in areas with a high prevalence of "Helicobacter pylori" (which normally inhabits the stomach wall and has been associated with peptic ulcers), identification and treatment of this infection has been shown to improve platelet counts in a third of patients. In a fifth, the platelet count normalized completely; this response rate is similar to that found in treatment with rituximab, which is more expensive and less safe. In children, this approach is not supported by evidence, except in high prevalence areas. Urea breath testing and stool antigen testing perform better than serology-based tests; moreover, serology may be false-positive after treatment with IVIG.

HPS was identified among healthy blood donors in the north-eastern part of the Indian subcontinent, characterized by absent bleeding symptoms, mild to severe thrombocytopenia (platelets rarely <50 X 109/L)with giant platelets (Mean platelet volume 10fL) and normal platelet aggregation studies with absent MYH9 mutation.

In the blood donors with HPS authors found a statistically higher MPV, RDW and a lower platelet count and platelet biomass.

At present the diagnosis of HPS is made by ascertaining the ethnicity of the patient, as well as assessing for conditions causing acquired thrombocytopenias, and after also excluding the known inherited giant platelet disorders(IGPD) and other congenital thrombocytopenias. Unfortunately some patients with IGPD are treated inappropriately with corticosteroids, immunoglobulin infusions and even splenectomy.

It is extremely important to recognize Harris platelet syndrome, as one third the population of certain parts of Indian subcontinent is affected.