Platelet

Platelets (from thrombos = clot and kytos = vessel, cover) are the smallest cells in the blood with a diameter of 1.5 µm to 3.0 µm. They are formed in the bone marrow by constriction from megakaryocytes.

The standard value is 150,000 to 380,000 per µl of blood.

The life span of platelets is 8-12 days.

The breakdown takes place mainly in the spleen; furthermore in the lungs and liver.

Thrombocytes are disc-like flat (discocytes), have no cell nuclei and thus no DNA structures, but mRNA from megakaryocytes. This enables them to synthesize new proteins. Like other cells, they also contain mitochondria, but a special form of the rough endoplasmic reticulum, the so-called "canalicular system". This serves as a calcium ion storage. Its rapid emptying into the cytosol is an essential prerequisite for physiological platelet aggregation. Further cell compartments of thrombocytes are the storage granules: they are called:

• alpha granules
• electron dense granules
• Lysosomes

and contain aggregation-promoting substances and proteins whose secretion is necessary for platelet function.

Normally platelets circulate freely in the blood. When they are activated (e.g. by exposed collagen in the case of an endothelial defect), reaction cascades are set in motion, which lead to the aggregation of the platelets at the defective site. In this process the platelet receptor, also known as glycoprotein receptor (GP IIb/IIIa), is transported from the cell interior to the cell surface. There it binds to fibrinogen or the von Willebrand factor (platelet adhesion). Through this process several thrombocytes are cross-linked with each other (platelet aggregation). This results in a three-dimensional network structure.

Remark: The platelet-receptor GP IIb/IIIa (GP = glycoprotein) belongs to the integrins. GP-IIb/IIIIa antibodies such as Tirofiban, or Abciximab are used as platelet aggregation inhibitors to suppress the formation of thrombocytes.

Deep vascular wall injuries and the release of lipid substances from atherosclerotic plaques lead to an increased release of tissue thromboplastin. By forming thrombin via the extrinsic pathway, tissue thromboplastin induces the plasmatic coagulation cascade and thus contributes to the activation of circulating platelets.

A congenital lack of special integrin receptors leads to a functional weakness in the aggregation ability of the thrombocytes(thrombasthenia Glanzmannn), which in turn causes a tendency to bleed.

The thrombocyte membrane also has receptors for adrenaline, ADP, collagen and arachidonic acid. These also modulate the aggregation ability of the thrombocytes.

When the thrombocytes are activated, they change their shape (shape change). Pseudopodia are protruding within seconds. This process is accompanied by a considerable increase in surface area. As a result, thrombus formation is intensified by fibrin-mediated binding with other thrombocytes. The endothelium in turn synthesizes factors that counteract platelet activation. These include prostacyclin, nitric oxide (NO) and heparin, which indirectly influences platelet activation by inhibiting thrombin activity.

The importance of this process is demonstrated in patients with mutations of the genes coding for vWF (von Willebrand-Jürgens syndrome) or for the receptor of the glycoprotein Ib-V-IX (Bernard-Soulier syndrome) (see also Urticaria aquagene). These patients have an increased tendency to bleed.

Standard value: The standard value in EDTA blood is between 150000 and 350000 /ul

Pathologically increased: acute and chronic inflammation, malignancies, after splenectomy, acute bleeding, post-operative, haemolysis, essential thrombocytopaenia, myeloproliferative diseases, chronic iron loss, glucorticoid therapy

Thrombopenia (causes and associated (skin) diseases):

• reduced formation in the bone marrow in blood diseases (e.g. acute myeloid leukaemia)
• Displacement of the bone marrow through diffuse tumor infiltration
• Osteomyelofibrosis
• Myelodysplasia
• due to increased turnover, shortened life time in case of disseminated intravascular coagulation (e.g. in case of sepsis)
• for splenomegaly
• Autoimmune disease: in case of autoantibodies against thrombocytes (e.g. autoimmune thrombocytopenia, Werlhof's disease),
• idiopathic thrombocytopenia
• Skin lesions associated with thrombocytopenia:
  • Dermatosis, acute febrile neutrophilic
  • dyskeratosis congenita
  • Fasciitis, eosinophilic
  • infant hemangioma
  • Heparin allergy
  • Heparin necrosis
  • immunodeficiencies, T-cellular, primary
  • Kasabakh-Merritt Syndrome
  • Livedo Syndromes
  • lymphohistiocytosis, familial hemophagocytic
  • Moschcowitz Syndrome
  • Panniculitis, histiocytic, cytophagic
  • Phospholipid antibody syndrome
  • Polyvinyl chloride disease
  • Pseudo-SLE Syndrome
  • Purpura, idiopathic thrombocytopenic
  • Wiskott-Aldrich syndrome (thrombocytopenia, familial with eczema and susceptibility to infection)

Thrombocytosis (causes and associated (skin) diseases):

• post- and para-inflammatory
• paraneoplastic (described in ovarian cancer and NM-Skin Cancer. In the case of ovarian carcinoma, it was also shown that, in addition to thrombocytosis, plasma levels of thrombopoietin and IL-6 were significantly elevated.
• in essential thrombocytosis
• in polycythemia vera
• after splenectomy
• Wiskott-Aldrich Syndrome
• Gray platelet syndrome
• Jacobsen Syndrome
• Skin lesions associated with thrombocytosis.
  • Erythromelalgia (which is associated with other microcirculatory disorders such as migraine-like symptoms and other ischemic events) is associated with essential thrombocythemia (ET), or polycythemia vera (PV). In these patients a shortened platelet survival is found in the laboratory. Serum levels of beta-thromboglobulin (beta-tg), platelet factor 4 (PF4), thrombomodulin (TM) level and thrombboxane B2 (TxB2) urinary excretion are also elevated.
  • Association with autoimmune diseases (rarely: systemic lupus erythematosus)
  • Adult breastfeeding syndrome
  • Kawasaki Syndrome
  • Livedo syndromes (livedovasculitis -Livedoracemosa-)
  • Gaucher's disease
  • POEMS Syndrome
  • Purpura Beauty Enoch
  • Schnitzler syndrome
  • Scleromyxoedema
  • Sneddon syndrome
  • Sweet Syndrome
  • Takayasu arteritis
  • Vasculitis, leukocytoclastic (non-IgA-associated)
  • Wegener's granulomatosis
  • Cellulite, eosinophil

Thrombocytopathies. These include:

• Bernard-Soulier syndrome
• von Willebrand-Jürgens-Syndrome
• Glanzmann thrombasthenia
• hereditary thrombasthenia
• Storage pool disease (reduction of dense granules with disturbance of irreversible platelet aggregation)

Platelet function - Diagnostics

The following parameters are available for the assessment of thrombocyte disorders:

• Platelet count
• Rumble-Leede-Test
• Bleeding time
• Determination of the Ristocetin factor.

Various platelet function tests:

• Thromboplastin time (Qucik/INR)
• Retention tests
• Shutter speed
• Aggregation test
• Adhesion test
• Activity test according to Grotemeyer
• Thrombelastogram
• Flow cytometry
  

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