Introduction

• Purpura is the appearance of small, flat, purple, red, brown or reddish-purple spots due to bleeding under the skin by small vessel damage
• Leukaemia is a type of blood cancer that disrupts the function and production of platelets; which are important for blood clotting, and a low platelet count is one of the causes of purpura (bleeding under the skin)

This article discusses purpura, leukaemia and the relationship between them. 

Understanding Purpura

Purpura is a symptom of a disease that leads to discolouration on the skin or mucous membranes like the mouth and throat. The colour differs depending on your skin tone. Darker skin tones usually appear more brown than red. The spots usually do not turn white when pressure is applied.

Types of Purpura

Purpura can be either thrombocytopenic or non-thrombocytopenic. 

Thrombocytopenic purpura occurs when there are fewer than normal platelets (thrombocytes) in the blood, which are essential for blood clotting. It is caused by autoimmune conditions like immune thrombocytopenia ( ITP), infections in the bloodstream, medications, and bone marrow diseases. 

Non-thrombocytopenic purpura is when the platelet count is normal, but other factors cause bleeding under the skin. Weak or inflamed blood vessels, inherited disorders like Ehlers Danlos, injury, medications, and ageing cause it. 

Other types of purpura are Heparin induced, Warfarin induced, and Disseminated Intravascular Coagulation (DIC). 

Mechanisms of Purpura formation

• In cases when purpura is caused by blood vessel fragility, the vessels may be weakened by age or sun exposure. Capillaries can also be inflamed by a disease called vasculitis. The tiny capillaries may bleed and the blood pools under the skin, hence the discolouration of the skin
• In blood coagulation disorders, the platelets are reduced or non-functioning. Platelets are important factors in blood clotting and prevent you from bleeding uncontrollably. When there is a deficiency, bleeding may also occur under the skin, causing purpura
  When there is a platelet dysfunction, such as in thrombotic thrombocytopenia (TTP) or leukaemia, platelets become fragments, reducing platelet numbers. Platelet deficiency will again cause bleeding, appearing as red, purple or brown spots under the skin

Leukaemia and its effects on blood cells

Human blood is made up of different cells:

• white blood cells 
• red blood cells platelets 

White blood cells are also called leukocytes and can be myelocytic or lymphocytic in origin. Leukaemia is a group of different types of blood cancers that are caused by the dysfunctional growth of developing white blood cells. It is classified as either acute or chronic based on how quickly it develops, and as myelocytic or lymphocytic based on the cell of origin. 

Leukaemia is usually caused by immature leukocytes, but there are other less common types, such as mature B-cell and T-cell leukaemias and NK cell-related leukaemias, that arise from mature white blood cells. 

Leukaemia occurs due to the malignant transformation of pluripotent (i.e. it can give rise to both myeloid and lymphoid precursors) blood stem cells. These immature cells can grow rapidly when transformed, leading to replacement and interference with the development and function of normal blood cells, leading to clinical symptoms. 

The bone marrow becomes full of immature white blood cells, leading to the production of less red blood cells and platelets, causing anaemia and thrombocytopenia. Impaired platelet production and function usually shows clinical symptoms like bleeding and excessive bruising.

Leukaemia-related factors leading to Purpura

Thrombocytopenia (Low platelet count):

Platelets are the smallest blood component produced from the very large bone marrow cells called megakaryocytes, and they play an important role in blood clot formation and bleeding (haemostasis).. Platelets stick to the injury site when stimulated, activate there and release substances, forming a plug. These coordinated series of events are the vital biological processes for wound healing.

As mentioned earlier, leukaemia is a disease that affects platelet production and maturation. On biopsy, a leukaemic bone marrow will have plenty of megakaryocytes and little mature, functioning platelets. One of the main symptoms of leukaemia is bleeding, and the main cause of this complication is thrombocytopenia and/or defective platelet function. 

Impaired activation and aggregation processes by platelets is usually associated with leukaemia. The bleeding is caused by the replacement of normal bone marrow cells with leukaemic cells and the inhibition of platelet stem cell functions.

Disordered coagulation

Coagulation is a process where liquid blood clots and forms a gel-like substance. It is an important step in healing injuries. Leukaemia can disrupt the body's natural clotting and anti-clotting factors, increasing the risk of both bleeding and blood clot formation. This can occur due to thrombocytopenia, DIC, and decreased levels of coagulation factors. 

Leukaemic cells also produce substances which interfere with the clotting process, like annexin II. It should be noted that coagulation diseases are also common in patients with leukaemia. This increases the risk of bleeding in leukaemia patients.

Bone marrow dysfunction

The bone marrow is a soft, spongy tissue found inside large bones like hips, thighs or ribs, responsible for producing blood cells (red, white, and platelets) and contains stem cells that can develop into various blood cell types. 

Leukaemia cells occupy the bone marrow in a diseased state, replacing or suppressing the function of cells that develop into normal blood cells. This interference with normal bone marrow cell function can lead to inadequate numbers of red blood cells (causing anaemia), normal white blood cells (increasing the risk of infection) and platelets (thrombocytopenia increasing the risk of bleeding). This is caused by either a direct, chemical-mediated effect of the leukaemic cells or an indirect effect via remodelling of the bone marrow environment. Either or both lead to the suppression of normal bone marrow function. 

Different types of leukaemia affect the development and function of various cells in the bone marrow, leading to a loss of support of normal blood-making processes.

Clinical presentation of Purpura in leukaemia

These are larger, non-blanching (meaning they don't turn white when pressed) red or purple patches on the skin, larger than 2 millimetres, also caused by bleeding under the skin. Common purpuric signs in leukaemia patients are:

• Petechiae on the skin, mucous membranes, and other areas. These are tiny, pinpoint red or purple spots on the skin, smaller than 2 millimeters, caused by bleeding under the skin
• Large bruising or ecchymosis
• Bleeding from other sites (gums, nosebleeds, gastrointestinal)

The severity and progression of purpura can vary depending on the type of leukaemia, its stage, and the individual's response to treatment. Purpura and bleeding issues can be early signs of leukaemia, although they can also be caused by other conditions. Treating the underlying leukaemia is the most effective way to prevent or reduce purpura and other bleeding problems.

Diagnosis and management

• Diagnostic approaches to assess purpura in leukaemia patients are:
  • Blood tests (complete blood count, coagulation profile)
  • Bone marrow biopsy to assess the types of cells present in the bone marrow
• Treatment strategies:
  • Managing thrombocytopenia with platelet transfusions
  • Treatment of underlying leukaemia (chemotherapy, bone marrow transplant)
  • Supportive care to control bleeding risk

Prognosis and outcomes

The prognosis for leukaemia patients with purpura depends on the type of leukaemia, its stage, and the patient's overall health. Poor prognosis indicators are:

• Advanced leukaemia: Purpura, especially when accompanied by other signs of advanced disease, suggests a poorer prognosis
• Specific leukaemia types: Certain leukaemia types, such as acute myeloid leukaemia (AML) and T-cell prolymphocytic leukaemia (T-PLL), may have a worse prognosis when associated with leukaemia cutis
• Extramedullary infiltrations: The presence of leukaemia cells outside the bone marrow (extramedullary infiltrations) can also indicate a poor prognosis
• Treatment resistance: If leukaemia is resistant to previous treatments, the prognosis may be worse

Treatment outcomes are based on quick treatment, monitoring and outcomes of treatment, long-term outlook and specific treatment approaches.

Summary

Leukaemia and purpuric manifestations are related because leukaemia affects the production of normal, functioning blood cells; platelets and causes bleeding. Purpura is a type of skin manifestation that occurs due to bleeding under the skin. 

It is important to address purpura as a sign of leukaemia, as excessive bleeding can cause organ damage. Future research and treatment to improve outcomes for leukaemia patients with purpura should be undertaken.