Acquired giant platelet syndrome:

-Idiopathic thrombocytopenic purpura (ITP):

ITP or immune thrombocytopenic purpura, is when a severe decrease in platelets number and purple coloring of the skin takes place.
The most common type of ITP is acute thrombocytopenic pupura affecting children where symptoms start suddenly and vanish within months or weeks. Most importantly, ITP has no need for treatment and medication and it occurs once.
On the other hand, the other type is chronic ITP which targets all ages. Moreover, the symptoms might need months, years or even all life to disappear. Unfortunately, chronic ITP might reoccur so a hematologist is necessary to keep a check.

-Myelodsyplastic syndrome (MDS)

MDS is also a type of cancer. To clarify, the blood stem cells, known as megakaryocytes in the case of platelets, are abnormal (dysplastic). Consequently, the defective platelets die soon after they emerge to the blood stream causing thrombocytopenia. In short, this leads to bleeding and bruising obviously.

Inherited giant platelet syndrome:

Thanks to molecular understanding of giant Platelets, many genetic disorders causing the inherited giant platelet syndrome are known. In fact, they can be autosomal dominant, recessive dominant, X-linked disorders, or of unknown cause.

-Abnormalities in platelet cytoskeleton

1. Autosomal Dominant macrothrombocytopenia with Leukocytes inclusions (MYH9 disorders)
A mutation in the gene called MYH9 on chromosome 22q12-13 encoding the non muscle myosin heavy chain-A (NMMHCA) is found in four syndromes: May-Hegglin anomaly (MHA), Fechtner (FTNS), Sebastian (SBS), and Epstein (EPS). However, they are distinct from each other according to granulocyte inclusion bodies absence or presence, and according to Alport manifestations such as deafness, cataracts and nephritis. This type results in mild bleeding.

-Abnormalities in GPIb/IX/V

1. Bernard-Soulier syndrome (BSS)
Having giant platelets, thrombocytopenia and long-lasting bleeding are all symptoms of having the autosomal recessive BSS. Normal platelets have receptors on the surface for von Will-ebrand factor, this allows the platelets to attach themselves on damaged vessel walls preventing bleeding. The receptors are glycoproteins GP (Ib)/IX/V complex, where the damage in these receptors causes BSS leading to constant bleeding. The cause of giant platelet is the defective cross linkage between GPIb/IX/V and actin cross-linking protein (filamin A). Besides, laboratory diagnosis of BSS is done by flow cytometry determination of platelet GPIb/IX/V expression.

2. Digeorge/Velocardiofacial syndrome
Mutation of the gene GP1BB at the level of chromosome 22q-11 where microdeletion occurs. This results in parathyroid and thyroid hypoplasia, cardiac abnormalities, cleft palate, and mental retardations.

-Abnormalities in transcription factors

1. X-linked macrothrombocytopenia with dyserythropoiesis
Here we must mention the missense mutation of the famous GATA-1 transcription factor at chromosome Xp11. GATA-1 plays a role in megakaryocytes and erythroid development and growth. In fact, the mutation here means less transcription and no expression of GPIb alpha, GPIb beta, GPIX and GPV; therefore, macrothrombocytopenia and continuous bleeding are the symptoms.
2. Paris-trousseau syndrome/Jacobsen syndrome
Microdeletion of transcription factor Fli1 at chromosome 11q23 causes metal retardation, facial and cardiac abnormalities. In these adjoining syndromes, giant platelets shows having alpha granules, and the bone marrow shows having numerous micro-megakaryocytes.

-Unknown causes

a- Gray platelet syndrome (GPS)
Giant platelets of this syndrome have no alpha granules thus they appear gray or colorless on stained peripheral blood smear (both Wright or MGG). This syndrome involves thrombocytopenia and myelofibrosis, the last is due to the lack of granules storing platelet derived stored factors which leaves to the bone marrow. Unfortunately, the genes responsible are not yet known.
b- Type 2B von Willebrand disease
Patients have long-lasting bleeding and giant platelets due to deficiency in von willebrand factor (VWF) present in blood cells to provoke clotting.