A Case of Chronic Thrombocytopenia in a 17-Year-Old Female

Roger Riley, MD, PhD; Asad Khan, MD; Shella Pai, MS, SH(ASCP); Laura Warmke, MD; Marcus Winkler, MD; William Gunning, PhD


Lab Med. 2019;50(4):406-420. 

In This Article


PLT Structure and Function

PLTs are small, disk-shaped, anuclear blood cells derived from the cytoplasm of megakaryocytes in the bone marrow. PLTs circulate in the peripheral blood at concentrations of 150,000 to 400,000 per μL and form an integral part of the hemostasis system. Despite their small size, PLTs play an essential role in hemostasis. Severe and even fatal bleeding disorders can result under circumstances of PLT dysfunction or inadequate number (thrombocytopenia). PLTs function in a complex series of reactions involving adhesion to extracellular matrices, adhesion to other PLTs (aggregation), and release of internal chemical mediators (degranulation). These reactions are integrated with numerous chemical mediators, especially those belonging to the coagulation and complement systems.[1,2] A PLT plug is formed when activated PLTs interact with elements of the coagulation system at the site of disruption of a vessel. Ultimately, a stable fibrin clot seals the vessel until healing can occur.

The small size of the PLT precludes elucidation of their detailed structure by light microscopy or phase-contrast light microscopy. Use of transmission EM reveals a complex internal structure composed of an external amorphous coat containing glycoproteins (glycocalyx), a bilayer cell membrane, a canalicular system with cisternae contiguous with the plasma membrane that open to the exterior (surface-connected canalicular system [SCCS]), a dense tubular system analogous to the sarcoplasmic reticulum of other cells, storage granules (dense granules and α-granules), microperoxisomes, lysozymes, mitochondria, glycogen particles, and an array of cytoskeletal filaments and microtubules (microtubule coil) along the circumference.[3–5]

Each PLT contains several δ (dense) granules that store adenosine diphosphate (ADP), adenosine triphosphate (ATP), calcium, polyphosphate, serotonin, and other compounds.[6,7] PLT δ-granules are part of a group of lysosome-related organelles (LORs) that include melanosomes, lytic granules of cytotoxic T cells and natural killer cells, lamellar bodies of pulmonary type II cells, basophil granules, Weibel-Palade bodies, and other organelles.[8]

The quantity of δ-granules in healthy individuals is poorly documented. The widely used reference range of 3 to 8 δ-granules per PLT is unsubstantiated in the literature. Several investigators have utilized mepacrine, a fluorescent dye selectively accumulated by δ-granules, to quantitate δ-bodies. This technique was used by Costa et al[9] to establish a mean value of 6.4 δ-granules per PLT. A slightly lower mean value of 5.44 was reported by Boneu and colleagues;[10] in contrast, Corash et al[11] discovered a range of 3.5 to 6.8.

Other investigators have counted dense granules on micrographs prepared with PLT transmission EM. A range of 3 to 5 δ-granules per PLT was reported by Rodman (oral communication; February 3, 1982), but a more recent study by Gunning and Calomeni[12] found a range of 4 to 6 δ-granules per PLT, with a lower cutoff value of 3.68. Hayward and collaborators[13] found no age or sex-related variation in number and reported a lower limit of 4.9 δ-granules per PLT.

In contrast, other recent studies have found lower numbers of δ-granules. A mean δ-granule per PLT reference range of 1.2 to 4.0 was reported in a study of 113 healthy blood donors,[14] and a study confined to children and young adults showed a range of 1.78 to 5.25 δ-granules per PLT, with a 5th percentile of 1.96 δ-granules per PLT and overall mean of 3.07 δ-granules per PLT.[15] Ongoing studies to standardize EM methodology and quantify δ-granules in larger populations of healthy individuals may clarify this issue in the near future.

Mature PLTs also contain 50 to 80 α-granules, which hold a wide variety of cargo proteins that are synthesized by the megakaryocyte and trafficked to the granule (ie, PLT factor 4, beta-thromboglobulin, PLT-derived growth factor [PDGF], thrombospondin, fibronectin, von Willebrand factor [vWF]), passively adsorbed by the plasma (ie, albumin, immunoglobulin [Ig]G), or actively taken up from the plasma by endocytosis (ie, fibrinogen, coagulation factor V).[16–18] Altogether, more than 300 substances are released from activated PLTs; however, it is not yet known whether this release occurs randomly or in a controlled, orchestrated manner.[19]

The plasma membrane of the PLT functions in the interactions of the PLT with other cells and components of the intercellular matrix. Also, the PLT plasma membrane provides the phospholipid surface necessary for the efficient function of the coagulation system. Although the bilayer composition of the PLT plasma membrane is similar to that of other human cells, it also has a unique surface coating of glycoprotein-rich material (glycocalyx). Several integral membrane glycoproteins important in PLT adhesion and aggregation ([eg, GPIb/IX, GPIIb/IIIa, and GPIIIb [IV]) presumably reside in the glycocalyx.[20,21] All of these structures are involved in the response of PLTs to specific activating agonists, which bind to the membrane glycoprotein receptors on the PLT surface or otherwise cause calcium ion mobilization and arachidonic acid processing. In turn, the subsequent release of storage granule contents from the activated PLTs and the formation of thromboxanes proceed to activate additional PLTs.[22]

Because of their ellipsoid shape, the long axis of a PLT is oriented along the direction of blood flow (axial orientation) in a stream with low shear forces. PLT activation by agonists (such as thrombin, epinephrine, collagen, and ADP) induces substantial changes in PLT structure with a resulting change in shape,[23] with sphering, the projection of pseudopodia, and cell swelling. If the activation stimulus is strong enough, the secretion of granule contents occurs.[24,25]

Inherited PLT Disorders (Congenital Disorders)

Inherited PLT function disorders are uncommon; however, they can be considered in patients with a lifelong history of mucocutaneous bleeding.[26,27] These disorders are heterogeneous and can involve abnormalities in the PLT-membrane receptors (Table 2) or intracellular organelles (Table 3) that cause defective adhesion, aggregation, and/or secretion.[28–30]

A subgroup of inherited PLT disorders arises from deficiencies in the number and contents of the PLT storage granules. These storage-pool deficiencies (SPDs) can involve the α-granules only (α-SPD), the δ-granules only (δ-SPD), or both types of granules (α-, δ-SPD).[31,32] As a group, SPDs are autosomally inherited and clinically present with a mild bleeding tendency, ecchymoses, mucosal membrane bleeding, easy bruising, spontaneous bruising, and heavy menses. Due to this presentation, inherited PLT disorders should be considered in adolescent girls with heavy menstrual bleeding[33,34] and in forensic investigations of presumed child abuse with bleeding and bruising.[35]

A thorough, comprehensive physical examination and medical history is a critical initial step in the evaluation of a patient with a suspected bleeding disorder.[36] Because patients may underestimate or exaggerate the nature and severity of their bleeding symptomatology, the use of a standardized questionnaire is recommended to obtain a complete and accurate personal and family history. The bleeding assessment tool (BAT), developed by the Joint vWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group of the International Society of Thrombosis and Hemostasis Scientific and Standardization Committee (ISTH/SSC), is the most widely used standardized bleeding questionnaire at this time.[37]

The next step in the evaluation of patients with suspected PLT function abnormality is a laboratory evaluation, including a complete cell count, microscopic examination of the peripheral blood smear, and screening tests of PLT function. The PLT Function Assay (PFA)–100 (Siemens AG) closure time, thromboelastography, and light-transmission PLT aggregometry are commonly available screening assays of PLT function.[38–43] Based on the findings of these tests, more specific tests can be performed, such as EM, lumiaggregometry, flow cytometry, and molecular studies.[44–46]

δ-storage-pool Deficiency. δ-SPD can be autosomal dominant or recessive in inheritance. Most patients show mild to moderate mucocutaneous bleeding, but in some patients, their disorder goes undetected. The bleeding time is increased, but the PLT count is normal and peripheral blood-smear examination shows unremarkable PLT morphology. The PFA-10 closure time is usually increased,[47–49] although the results of one study[50] showed no correlation of the closure time with the severity of the disease as determined by EM. Light-transmission aggregometry typically show an impaired response to PLT-aggregating agents, with absence of a second wave of aggregation in response to ADP and epinephrine and a diminished response to low doses of collagen.[51,52] However, the reported sensitivity of conventional light-transmission PLT aggregometry for δ-storage pool deficiency is relatively low, with 25% to greater than 50% of patients showing a normal PLT-aggregation response.[13,53]

Also, the results of some studies have shown no statistical correlation between light-transmission aggregometry findings and the severity of clinical symptomatology or the number of δ-granules identified by light microscopy.[53] The reliability of diagnosing δ-SPD via whole-blood aggregometry measuring the secretion of PLT ATP has been recently called into question because variable findings have been reported by different laboratories, and the results do not show a significant relationship to clinical symptomatology or bleeding scores.[13,54] The use of additional agonists, such as the thromboxane A2 analog U46619, as well as ongoing efforts by the ISTH/SSC, Clinical and Laboratory Standards Institute (CLSI), and other organizations to standardize PLT-aggregation methodology among medical laboratories, may improve the sensitivity of this PLT aggregometry in the future.[53,55–57]

Transmission EM is the standard technique for the quantitation of PLT δ-granules. The electron microscope has been used since the early 1950s to study the ultrastructural features of PLTs; however, but James G. White, MD, of the University of Minnesota, pioneered the application of this technique for the clinical diagnosis of PLT disorders.[58–60] Conventional EM, performed on thin sections of fixed, resin-embedded PLTs, reveals information about all organelles and granules, as well as microtubules and cell membranes. However, δ granules are electron dense and can be easily visualized and counted by whole-mount EM performed on unfixed PLTs.[61] EM reveals an absence or marked deficiency in the number of δ-granules in δ-storage pool deficiency, although the diagnostic interpretation of patient specimens is hampered by the lack of procedural standardization and a validated δ-granule reference range.[13,59,62] Lumiaggregometry, whole-blood aggregometry, serotonin release, flow cytometry, and other assays of PLT secretion have been used experimentally and are also available from specialized reference laboratories for patient care.[39,43,45,51,63]

A deficiency of PLT δ-granules is a component of several inherited diseases in addition to δ storage-pool deficiency and combined α- and δ-storage-pool deficiency. These diseases include Hermansky-Pudlak syndrome (HPS), Chédiak-Higashi syndrome, Wiscott-Aldrich syndrome (WAS), thrombocytopenia with absent radii (TAR) syndrome, Ehlers-Danlos syndrome (EDS) type IV, orthostatic tachycardia syndrome (POTS), Griscelli syndrome type 2, osteogenesis imperfecta, Jacobsen/Paris-Trouseau syndrome, and Medich giant PLT syndrome.[64–67]

HPS is a heterogeneous group of autosomally recessively inherited disorders. Genetic mutations in 9 genes have been identified in individuals with HPS, resulting in 9 recognized subtypes.[68] Recently, a new potential subtype of HPS with the proposed acronym HSP10 (AP3D1, 19p13) has been described.[69] HPS is most common in individuals of Puerto Rican descent and has an overall prevalence of 1:500,000 to 1:1,000,000. The disorder is marked by the deposition of ceroid-lipofuscin storage material in cells of the reticuloendothelial system; patients present with associated oculocutaneous albinism, pulmonary fibrosis, colitis, and variably severe bleeding tendency.[70,71] δ-granule deficiency is a component of the Chediak-Higashi syndrome, caused by mutations in the CHS1/LYST gene that lead to abnormal lysosome trafficking.[72,73]

WAS is an X-linked disorder arising from mutations in the WASP gene. The patients with this disorder have variable bleeding manifestations with microthrombocytopenia and reductions in PLT δ-granules, α-granules, and mitochondria.[66] TAR syndrome is characterized by hypomegakaryocytic thrombocytopenia with skeletal deformaities and decreased dense granules.[66,74] EDS is a group of inherited connective-tissue disorders with joint hypermobility, skin hyperelasticity, and easy bruising. PLT δ-storage-pool deficiency has been identified as a component of type IV EDS.[75]

POTS is a disease of unclear etiology characterized by orthostatic intolerance and a variety of other clinical symptoms, including bleeding diathesis.[76] Gunning et al[77] identified δ-storage-pool deficiency in the majority of the members of a cohort of patients with PoTS who had bleeding symptoms. PoTS is also associated with joint hypermobility syndrome (ie, EDS hypermobility type, EDS type III), and other diseases.[78,79]

Griscelli syndrome, type 2, occurs due to an autosomal recessive mutation in the RAB27A gene, leading to immunodeficiency in and abnormalities of the skin and hair. Many patients eventually develop an accelerated phase involving hemophagocytic lymphohistiocytosis (HLH).[74]

PLT δ-granule deficiency has been reported as a component of Jacobsen syndrome, a congenital macrothrombocytopenia that occurs due to a large 11q23 terminal deletion encoding the FLI1 gene.[80,81] Patients with Jacobsen syndrome also have giant PLT α-granules, intellectual and developmental disabilities, trigonocephaly, facial dysmorphism, and cardiac anomalies. A related disease, Paris-Trousseau syndrome, occurs due to a smaller mutation that produces macrothrombocytpenia, PLT dysfunction, and giant-PLT α- granules but not the severe manifestations of Jacobsen syndrome.[82] White[80] reported PLT δ-granule deficiency confined to Jacobsen syndrome.

α-storage-pool Deficiency. PLT α-SPD was first reported by Raccuglia at the University of Louisville in 1971.[83] Since then, more than 60 additional cases have been described in the literature.

Clinical Characteristics

The clinical features of patients with α-SPD have been elucidated from individual case reports and a few larger cohort studies. In most cases, thrombocytopenia and easy bruising are noted in early childhood and are often accompanied by epistaxis and increased bleeding after trauma, surgical procedures, or dental procedures. Intracranial hemorrhage has rarely been reported. In female patients, heavy menstrual bleeding at menarche may herald the onset of α-SPD.

One of the largest cohort studies of α-SPD[84] reported a detailed clinical, laboratory, and genetic analysis of 114 individuals from 14 families with α-SPD, including 25 patients with GPS. Most patients in the study demonstrated bleeding tendency from the neonatal period to early childhood, with symptoms occurring at an average age of 2.6 years. Bleeding tendency varied, from mild (37%) to moderate (21%) and severe (42%). Seven of the 8 cases of severe bleeding occurred in women with menorrhagia who developed severe iron-deficiency anemia. Thrombocytopenia was variable and inversely correlated with patient age. For patients with thrombocytopenia, an initial diagnosis of idiopathic thrombocytopenia was made in more than 50% of the patients.

Serial bone marrow studies in several patients revealed variable reticulin fibrosis that developed in adulthood and increased in severity with age. Splenomegaly was discovered in 88% of the patients, and markedly elevated vitamin B12 levels were reported in 92%. No abnormalities were found in the prothrombin time (PT) or the activated partial thromboplastin time (aPTT). Liver, kidney, and thyroid function were all within normal limits.

Diagnosis and Laboratory Testing

The clinical history of bleeding diathesis usually elicits blood cell counts and the finding of thrombocytopenia with an elevated mean PLT volume (MPV). Differential considerations at this stage of the evaluation include different types if macrothrombocytopenia (Bernard-Soulier syndrome, MYH[myosin heavy chain]9–related thrombocytopenia, ITP, and other diseases.

The finding of large, gray, hypogranular PLTs on the peripheral blood smear is characteristic of α-SPD; however, other conditions in which abnormal, degranulated PLTs can be found must be excluded. Several conditions in which degranuated PLTs can be found include pseudo-GPS, myeloid neoplasms, myelodysplastic syndrome, and α- and δ-granule deficiency, White PLT syndrome, Medich giant-PLT disorder, Quebec PLT disorder, and other autosomal and X-linked forms of thrombocytopenia with α-granule abnormalities.[41,85] The results of PLT aggregation studies may be normal or may show absence of a second wave of aggregation to ADP and epinephrine, with a decreased response to thrombin and low concentrations of collagen.

As previously mentioned herein, within the differential diagnosis of α-SPD and, more specifically, GPS, is a condition called pseudo-GPS. This rare acquired condition occurs due to in vitro PLT degranulation when using collection tubes with the anticoagulant ethylenediaminetetraacetic acid (EDTA).[86–88] Although EDTA is well known to cause pseudo-thrombocytopenia, a lesser-known anomaly involves EDTA-induced pseudo-storage-pool disease.[89] It is thought that EDTA initiates PLT activation by a plasma factor that is not an Ig, fibrinogen, or albumin; however, the exact cause remains unknown.[90] Degranulation after EDTA-involved blood collection is usually complete within 60 minutes.[91] Microscopically, the PLTs are large and agranular with gray, pale-blue cytoplasm, thus mimicking GPS.[92] The PLT count may be falsely decreased, and the MPV may be falsely elevated.

EM can confirm EDTA-induced degranulation by demonstrating PLTs with a markedly decreased amount of storage granules. The phenomenon of pseudo-GPS does not occur in specimens anticoagulated with citrate, heparin, or the mixture citrate theophylline adenine dipyridamole.[93] Because this finding is artifactual, the PLTs should function normally in vivo. Patients with pseudo-GPS frequently do not have a clinical history of bleeding, and whole blood from these patients may be drawn in a vacuum tube containing sodium citrate, enabling accurate automated-analyzer analysis and peripheral smear morphologic evaluation.

A definitive diagnosis of α-SPD requires ultrastructural demonstration of an absence or marked reduction in PLT α-granules.[60] Ultrastructural examination using transmission EM was first reported by White in 1979[94] and by Breton-Gorius in 1980,[95] and was subsequently confirmed by other investigators.[96] In α-SPD, PLT EM characteristically shows a lack of α-granules, and δ-granules and other PLT organelles are within normal limits. Corresponding to the deficiency of α-granules, there is also a quantitative deficit of α-granule storage components.[97]

We were surprised to discover that in some patients with α-SPD, acquired abnormalities in other PLT components have been reported. Such abnormalities include decreased surface membrane expression of P-selectin, TSP-1, collagen (glycoprotein VI) receptor, and fibrinogen receptor.[98] Although several PLT component abnormalities have been described, secretory granules in neutrophils appear structurally normal, although some abnormalities have been reported.[99,100]

Besides ultrastructural examination by EM, flow-cytometric analysis has been described as another method for detecting α-SPD.[63,101] Additional laboratory findings include an elevated serum vitamin B12 level that is characteristic but not specific for α-SPD. Elevated vitamin B12 levels have also been reported in myeloproliferative disorders, hypereosinophilic syndrome, hepatic disease, and various cancers (liver, lung, and colon). Although bone-marrow evaluation is not required to make the diagnosis of α-SPD, it is necessary to monitor for the potential development and progression of secondary myelofibrosis. Bone-marrow examination usually reveals the presence of agranular megakaryocytes.


Clues to the pathogenesis of α-SPD, and more specifically GPS, first arose from studies using EM, immuno-EM, immunocytochemistry, and other techniques. One early discovery occurred when Breton-Gorius et al[95] performed ultrastructural studies on megakaryocytes from 2 patients with GPS. The immature megakaryocytes of these patients contained small rudimentary α-granule precursors. The contents of the precursors were discharged with further cell maturation, and fully formed α-granules never developed. The remnants of the early α-granules remained as distended demarcation membranes and vacuoles; they were termed ghost granules by Maynard et al.[102]

These initial findings were later augmented by the findings of Rosa et al.[103] Using antibodies against the α-granule membrane protein GMP-140, the researchers identified intracellular vesicles within gray PLTs that contained normal amounts of GMP-140. With PLT activation, the GMP-140 was further normally redistributed to the surface. Despite normal GMP-140 levels, the endogenously synthesized cargo protein PLT factor 4 was undetectable, leading to the hypothesis that a defect in the transfer of endogenously synthesized secretory proteins into developing α-granules within the megakaryocyte was the cause of α-SPD. Further evidence to support this theory was provided by Maynard et al,[102] who used immuno-EM to demonstrate the severe reduction or absence of several endogenously synthesized cargo proteins in gray PLTs, including the newly discovered α-granule protein latent transforming growth factor beta binding protein 1 (LTBP-1).

Additional studies have provided further evidence that the defect in α-SPD is confined to the megakaryocyte. For example, the findings of an ultrastructural study of the Weibel-Palade secretory organelles of the dermal capillary endothelial cells in patients with α-SPD showed normal content and distribution of vWF and P-selectin.[104]

More recently, genetic and molecular studies by authors such as Pluthero et al[105] have added to the original clinical and structural observations. From a genetic standpoint, GPS has most commonly been described in male and female patients, whose parents are usually unaffected. This pattern is most consistent with an autosomal recessive pattern of inheritance. The genetic cause of GPS was first identified in 2010, when Gunay-Aygun[84] and coworkers used genome-wide linkage analysis of a cohort of patients with autosomal recessive GPS, to map the mutant gene to a 9.4-Mb interval on 3p21.1–3p22.1.

Further studies by Gunay-Aygun et al and by 2 other groups of investigators[106,107] independently confirmed that the NBEAL2 (neurobeachin-like 2) gene was mutated in all patients studied with autosomal recessive GPS. This finding was additionally confirmed in an NBEAL2-knockout mice model. The product of the NBEAL2 gene is a 302-kDa protein, NBEAL2, and a member of the BEACH-WD40 domain. NBEAL2 is 1 of 9 proteins that currently comprise the BEACH (BEige And Chédiak-Higashi) domain-containing proteins (BDCPs).[108] The other members of this family include the lysosomal trafficking regulator (LYST) protein, neurobeachin (NBEA), neurobeachin-like 1 (NBEAL1), lipopolysaccharide-responsive, beige-like anchor protein (LRBA), WD and FYVE zinc finger domain-containing protein 3 (WDFY3), WD and FYVE zinc finger domain-containing protein 4 (WDFY4), neutral sphingomyelinase activation-associated factor (NSMAF), and WD repeat domain 81 (WDR81).[109]

In addition to BEACH and WD40, the BDCPs contain combinations of other domains, including PH (pleckstrin homology), Con A (Concanavalin A) lectin, DUF1088 (domain of unknown fuction 1088), ARM (armadillo), FYVE (FYVE zinc finger domain), and GRAM domain (GRAM). These proteins are involved in a wide variety of cellular functions, including membrane dynamics, protein trafficking, and vesicular transport, and have also been reported to have mutations in several other human diseases. The precise mechanism through which NBEAL2 mutations lead to defective α-granule formation is still under investigation. A recently proposed hypothesis is that BDCPs play an essential role as scaffold proteins to regulate membrane properties and functions, such as granule size, lysosome size, apoptosis, autophagy, and synapse formation. According to this hypothesis, the exact function of each BDCP is determined by its domain structure and binding partner.[109]

A common complication of GPS is the development of myelofibrosis. Fibrosis within the bone marrow has been attributed to the loss of PDGF, PF4 (PLT factor 4), and other profibrotic substances from megakaryocytes into the bone-marrow microenvironment, with the stimulation of fibroblast proliferation.[110,111] In a murine knockout GPS model, Guerrero and coworkers[112] also discovered that the lack of NBEAL2 confers a proinflammatory phenotype to the bone-marrow megakaryocytes that exacerbates the myelofibrosis. This hypothesis is supported by the results of microarray studies that demonstrated increased expression of fibronectin and other cytoskeleton-related proteins in the fibroblasts of a patient with α-SPD.[84]

Although NBEAL2 is the major source of mutations in GPS, other gene variants have been described that result in significant α-granule deficiencies in PLTs. Gene variants include mutations in GATA1, VPS33B, VIPAS39, and GFI1B.[113]

GATA1 is a transcription factor that is important for erythropoiesis, megakaryopoiesis, and the control of NBEAL2 expression.[114] Two rare X-linked mutations in GATA1 have been described with macrothrombocytopenia and PLT α-granule deficiency. Dyserythropoietic anemia with thrombocytopenia has been reported in several families with different GATA1 mutations, and X-linked thrombocytopenia with thalassemia has been identified in several patients with a GATA1 Arg216Gln mutation.[115–119] These GATA1-related syndromes differ from GPS in that they show X-linked inheritance and dyserthropoiesis with features similar to β thalassemia. Another rare disorder, arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, shows a complete absence of α- granules with mutations in VPS33B and VIPAS39.[120] Similar to GPS, this disorder shows autosomal recessive inheritance; however, it is further characterized by arthrogryposis, renal dysfunction, and cholestasis, all of which are absent in GPS. Lastly, mutations in GF1B show a mix of normal PLTs with α-granule deficient ones; the inheritance pattern is autosomal dominant. Overall, it has been proposed[121] that these disorders should not be classified as types of GPS.

Treatment and Prognosis

The prognosis of patients with GPS depends on the PLT count and is usually good in mild disease with a PLT count greater than 30,000 per μL. The treatment of patients with GPS is similar to that of other inherited PLT-function diseases in that a definitive treatment is not available; treatment is supportive and preventative in nature.[122]

Patients are educated to avoid trauma and high-risk activities. Patients are further instructed to avoid intake of foods and drugs that compromise PLT function. PLT transfusions are used to control significant bleeding episodes and may be administered prophylactically before surgery. DDAVP (1-desamino-8-D-arginine-vasopressin, desmopressin) and antifibrinolytic agents, such as aminocaproic acid, are beneficial in some patients. Treatment with recombinant Factor VIIa is an option in the event of severe bleeding or PLT alloimmunization.