Introduction

Purpura refers to purple-coloured patches and spots that occur on the skin and mucous membranes, such as the mouth lining, as a result of haemorrhage from small blood vessels bleeding beneath the skin.^1,2,3 They are typically 4 to 10 millimetres in diameter, while smaller lesions (less than 4 mm) are called petechiae and larger lesions (larger than 1 cm) are ecchymoses or bruises.^1,3 Purpura, due to the leaking of blood, breaks down and changes colour over several weeks, changing from purple to orange, brown, and even blue and green.³ The causes of purpura can be divided into a broad category based on whether they are disorders of platelets, vascular disorders, or other coagulation disorders.³ The platelet disorder and vascular disorder aspects of Purpura shall be addressed in this article as we delve into Thrombocytopenic purpura and Nonthrombocytopenic purpura. 

The clinical significance of purpura is that it is a palpable indication that the small blood vessels are bleeding.¹ While purpura itself is not harmful, it can be a symptom of a condition that requires treatment. Thrombocytopenic purpura, for example, signifies that the body has an issue with blood clotting due to insufficient platelets and can exhibit itself in the form of easy bruising, bleeding gums, nosebleeds, blood in the urine or stools, and excessive menstrual flow.^2,4 While Non-thrombocytopenic purpura can signal blood vessel integrity problems or inflammation or be associated with other underlying medical conditions like autoimmune diseases or infections, with or without the presence of other symptoms like itchiness, joint pain, abdominal pain, or fever.³ The difference between thrombocytopenic and non-thrombocytopenic purpura is significant as it will narrow the number of potential causes and guide the diagnostic and therapeutic approaches.² Treatment for thrombocytopenic purpura is typically intended to increase platelet count or decrease platelet destruction ², while treatment for non-thrombocytopenic purpura is intended to cure the primary disease.^2,3

Understanding Purpura

Pathophysiology

Purpura is characterised by purple spots and patches on the skin and mucous membranes due to haemorrhage from small blood vessels^1,2 It occurs when small blood vessels leak blood under the skin.¹ The underlying pathophysiology can be broadly categorised based on platelet counts.^1,2

Capillary leakage: Purpura is due to the leakage of blood from the walls of small blood vessels, so that blood accumulates outside the blood vessels, a process known as extravasation.^1,3 This can happen even though the platelet count is normal (non-thrombocytopenic purpura) or when the platelet count is reduced (thrombocytopenic purpura).^1,2

In thrombocytopenic purpura (TP), the basic issue is an abnormally low platelet count (thrombocytopenia).^2,4 Platelets are responsible for blood clotting, and when there are fewer of them, the body loses the ability to stop bleeding from injured small vessels and thus gets purpura.⁴ This may be due to the immune system attacking and destroying platelets (e.g., in Immune Thrombocytopenic Purpura - ITP),^2,4 formation of small blood clots inside the body that consume platelets (e.g., in Thrombotic Thrombocytopenic Purpura - TTP),² drugs that lower platelet counts, infections in the bloodstream (e.g., meningococcemia),^1,2,4 or autoimmune disorders. In ITP, immune destruction is typically secondary to antibody production against platelets. Less commonly, T-cells attack platelets directly.

In non-thrombocytopenic purpura (NTP), platelet counts are normal, and purpura is caused by escape of blood into the vessel wall.³ This can be due to damage to small blood vessels, increased pressure in blood vessels, inadequate support for blood vessels (in aged or sun-damaged skin - senile or actinic purpura),^2,3 vasculitis, certain drugs (e.g., corticosteroids), coagulation disorders of the blood, aging, vitamin C deficiency (scurvy),^1,2 certain infections, changes in pressure during labor, amyloidosis, or a hemangioma.

Clinical presentation

The clinical presentation of purpura is based on the type of lesions and associated symptoms.

• Petechiae are described as small, red or purple skin spots, often less than 2-4 mm in diameter, due to bleeding from minor vessels.^1,2,3 Petechiae most commonly occur in association with a reduced platelet count (thrombocytopenia).^2,3 Petechiae in Immune Thrombocytopenic Purpura (ITP) can be an indication because the blood has impaired ability to coagulate effectively⁴ 
• Ecchymoses, or bruises, are larger areas of skin colour change (purple, orange, brown, blue, or green) due to extravasation of blood from blood vessels.^1,3 They can be caused by platelet disorders or other coagulation disorders.³ Easy bruising is a manifestation of ITP⁴
• Palpable purpura is a significant finding that helps to distinguish certain types of purpura. It refers to a purpuric rash that can be felt on examination.³ It typically indicates inflammation of blood vessels (vasculitis)^1,3 

Diagnostic considerations

The presence of different clinical presentations of purpura suggests a potential complex clinical picture that can be caused by platelet abnormalities and inflammatory vascular disease. Therefore, consideration in diagnosis needs to include testing for non-thrombocytopenic and thrombocytopenic purpura causes.

1. Platelet Count Evaluation: Petechiae and ecchymoses typically raise suspicion of thrombocytopenia. A CBC is a valuable initial test to determine the platelet count.^2,4 A decreased platelet count would lead to a thrombocytopenic purpura, e.g., ITP.^1,2 The red and white blood cell counts are normal in ITP, but the platelet count is low.⁴ A peripheral blood smear can be used as a follow-up to an abnormal CBC to assess the platelets⁴ 
2. Evaluation for Vasculitis: Palpable purpura is very suggestive of vasculitis, a non-thrombocytopenic purpura caused by inflammation of vessels.^1,2,3 The considerations in the diagnosis of vasculitis include:

• Complete Medical History and Physical Examination: Assessing for other symptoms and signs of systemic involvement, as vasculitis can be associated with many underlying conditions like infections, autoimmune disorders (e.g., lupus, rheumatoid arthritis), and medications.^1,3,4 
• Skin Biopsy: Biopsy of the palpable purpuric lesions is generally necessary to diagnose vasculitis by examining the blood vessels for inflammation^1,3 
• Blood and Urine Tests: These may be requested to look for signs of inflammation, autoantibodies, and to assess organ function, which can be affected in systemic vasculitis^1,4 

3. Bone Marrow Test: In some cases of thrombocytopenic purpura, a bone marrow test is performed to determine if the bone marrow is in good condition and yielding sufficient platelets, and to rule out other haematological disorders.²,⁴

Thrombocytopenic Purpura

Thrombocytopenic Purpura (TP) is a purpura condition that is accompanied by a reduced platelet count (thrombocytopenia).

Common causes

Typical causes of thrombocytopenic purpura include:

• Immune Thrombocytopenic Purpura (ITP): This is an autoimmune condition in which the immune system destroys and attacks platelets, leading to a low platelet count.² ITP is either acute, which is more common in young children and often follows a virus like chickenpox, and the symptoms will usually resolve by six months.⁴ It can be chronic, lasting over six months and affecting adults and adolescents, with a greater number of women than men⁴
• Drug-induced thrombocytopenia: Certain drugs can decrease the platelet count, leading to TP.² This is possibly due to an allergic reaction that cross-reacts with platelets⁴
• Infections: Certain viral infections, such as those causing chickenpox, hepatitis C, and AIDS, can induce the immune response leading to ITP.²,⁴ Meningococcemia, a severe bacterial infection, can also lead to TP¹,²

Laboratory findings

Lab results for TP, usually show low platelet counts.^2,4 Normal platelet count is between about 150,000 to 450,000 per microliter (µL) of blood and in ITP, platelet counts are less than 100,000.⁴ One of the primary tests used to assess the platelet count is a complete blood count (CBC).^2,4 Peripheral blood smear may be performed as a follow-up to examine the platelets. Bone marrow tests can also be done to find out if the bone marrow is normal and producing platelets in abundance.^2,4

Clinical features

The signs of thrombocytopenic purpura are related to uncontrolled bleeding due to a low platelet count. Some of these may be:

• Bruises or purple patches on the skin.
• Mucous surface bleeding, i.e., nosebleeds, and gum and mouth bleeding^2,4
• Heavy Menstrual bleeding^2,4
• Gastrointestinal bleeding, i.e., spitting up blood, bleeding in urine, or stools⁴
• Fatigue⁴
• The most dangerous sign of ITP is intracranial haemorrhage, which is life-threatening, especially following head injury⁴

Management

Management of thrombocytopenic purpura involves:

• Treatment of the underlying cause: If a drug or infection is the underlying cause, these factors must be treated²,⁴
• Platelet transfusion: In severe bleeding or before surgery, it can be administered⁴
• For Immune Thrombocytopenic Purpura (ITP), immediate therapies are usually:
• Corticosteroids: These medications stop bleeding by lowering platelet destruction and can lead to an increased platelet count²,⁴

Intravenous immunoglobulin (IVIG): This consists of antibodies obtained from healthy donors and is used to increase the platelet count, typically with response within 24 to 48 hours.²,⁴

Non-thrombocytopenic Purpura

Non-Thrombocytopenic Purpura (NTP) is one type of purpura, but with a normal platelet level. In NTP, the normal platelet level implies that the bleeding is not due to a deficiency in platelets but due to some issue with the blood vessels themselves or something else.¹,² 

Common causes

Common causes of non-thrombocytopenic purpura include:

• Vasculitis, which includes Henoch-Schönlein purpura, is an important cause, characterised by inflammation of the blood vessels. Henoch-Schönlein purpura is a cause of non-thrombocytopenic purpura and creates a raised/palpable form of purpura¹,²
• Trauma or mechanical cause, like injury. Purpura results from injury¹,^{2 ,3} 
• Immune disorders like rheumatoid arthritis and lupus as potential causes of immune thrombocytopenic purpura. Autoimmune diseases like lupus can cause purpura
• Amyloidosis, a disease in which tissues and organs deposit abnormal proteins, is also a cause of non-thrombocytopenic purpura¹
• Infections with cytomegalovirus (CMV), rubella, Epstein-Barr virus and other infections pose potential causes of non-thrombocytopenic purpura¹,² 
• Drugs are also accused as a causative factor, perhaps through vascular damage or by affecting platelet function or clotting factors. Medications that affect platelet function or clotting factors, and cites some drugs like corticosteroids as a causative factor¹,² 
• Other causes include fragile vessels of the elderly (senile purpura), increased intraluminal pressure, poor vascular support, the use of steroids, vaginal delivery pressure changes, and vitamin C deficiency (scurvy)¹,^2,3 

Clinical features

• Palpable purpura is a manifestation of NTP, particularly in vasculitis³ 
• Abdominal complaints and arthralgia are included as potential symptoms of NTP, according to aetiology.¹,²
• Other signs of NTP may be itching on or close to the discoloured patches, fever or illness resembling the flu, diarrhoea, hives, and other signs, depending on the underlying disease²

Management

• For vasculitis, corticosteroids may be used as treatment to repress the immune system. Immunosuppressive medication may also be used in autoimmune diseases that result in NTP²
• Symptomatic treatment can be used for NTP.² In mild cases, NTP may heal spontaneously without treatment.² Topical creams contain alpha-hydroxy acid, retinol, and arnica oil to stimulate circulation and thicken the skin in some cases of NTP. Over-the-counter analgesics and anti-inflammatory medications can also be used to treat pain and inflammation²
• Avoidance of causative agents is essential. This involves halting or reducing the dose of causative medications that produce purpura. In case the purpura results from an infection, antibiotics or antiviral drugs are administered²

Key Differences between Thrombocytopenic and Non-thrombocytopenic Purpura

Summary

Purpura refers to the presence of purple spots or patches on the mucous membrane or skin as a result of intracutaneous bleeding. Purpura does not constitute a diagnosis but is a clinical observation and usually reflects the existence of a disorder of the hematologic, vascular, infectious, or systemic nature. Clinically, purpura can be classified based on the number of platelets into two broad categories: thrombocytopenic purpura and non-thrombocytopenic purpura.

Thrombocytopenic purpura results from a reduction in the number of circulating platelets, resulting in impaired primary hemostasis and spontaneous capillary haemorrhage. Thrombocytopenic purpura is most commonly found in conditions of immune thrombocytopenic purpura (ITP), drug-induced thrombocytopenia, bone marrow suppression, and systemic infections. Petechiae are generalised, mucosal haemorrhage occurs, and in some extensive cases, there is internal haemorrhage. Non-thrombocytopenic purpura, on the other hand, is seen with normal platelet counts and typically is due to increased vessel fragility or inflammation. Causes include vasculitis (e.g., Henoch-Schönlein purpura), connective tissue disease, age (senile purpura), and nutritional deficiencies such as scurvy. Palpable purpura, especially over dependent areas, can occur, and systemic findings such as arthralgia or hematuria can also occur, depending on the aetiology.

The two are clinically very significant to be differentiated, as the strategy of diagnosis, treatment plan, and prognosis is significantly different. A thorough history of the patient, clinical evaluation, and judicious investigations like complete blood count, coagulation studies, inflammatory markers, and skin biopsy are required in arriving at a proper diagnosis.

Lastly, the occurrence of purpura must prompt immediate medical evaluation. Physicians must also be sensitive to warning signs calling for referral to a specialist emergently, such as profuse bleeding, systemic disease, or suspected hematologic malignancy or autoimmune illness. Early and appropriate diagnosis ensures effective treatment, reduces the risk of complications, and improves patient outcomes.