To minimise the risks associated with splenectomy, antibiotic and vaccination protocols have been established, but are often poorly adhered to by physicians and patients due to the complications resulting from antibiotic prophylaxis such as development of an overpopulation of Clostridium difficile in the intestinal tract.

In addition to the normal immunizations advised for the countries to be visited, Group A meningococcus should be included if visiting countries of particular risk (e.g. sub-saharan Africa). The non-conjugated Meningitis A and C vaccines usually used for this purpose give only 3 years coverage and provide less-effective long-term cover for Meningitis C than the conjugated form already mentioned.

Those lacking a functional spleen are at higher risk of contracting malaria, and succumbing to its effects. Travel to malarial areas will carry greater risks and is best avoided. Travellers should take the most appropriate anti-malarial prophylaxis medication and be extra vigilant over measures to prevent mosquito bites.

The pneumococcal vaccinations may not cover some of the other strains of pneumococcal bacteria present in other countries. Likewise their antibiotic resistance may also vary, requiring a different choice of stand-by antibiotic.

Asplenia is the absence of normal spleen function. It predisposes to some septicemia infections. Therefore, vaccination and antibiotic measures are essential in such cases. There are multiple causes:

- Some people congenitally completely lack a spleen, although this is rare.

- Sickle-cell disease can cause a functional asplenia (or autosplenectomy) by causing infarctions of the spleen during repeated sickle-cell crises.

- It may be removed surgically (known as a splenectomy), but this is rarely performed, as it carries a high risk of infection and other adverse effects. Indications include following abdominal injuries with rupture and hemorrhage of the spleen, or in the treatment of certain blood diseases (Idiopathic thrombocytopenic purpura, hereditary spherocytosis, etc.), certain forms of lymphoma or for the removal of splenic tumors or cysts.

Pneumococcal septicemia, or whole-body infection caused by the "Streptococcus pneumoniae" bacteria, has been reported to cause autosplenectomy but is a very rare and poorly understood complication of the infection.

Absence of effective splenic function or absence of the whole spleen (asplenia) is associated with increased risks of overwhelming post splenectomy infection, especially from polysaccharide encapsulated bacteria and organisms that invade erythrocytes. People without a spleen have a weakened immune system, although other immune organs compensate for the missing spleen. Vaccination against encapsulated bacteria and prophylactic antibiotics can be used to counteract lowered immunity in asplenic patients. Specifically, people without a spleen are recommended to be vaccinated against pneumonia, influenza, Haemophilus influenza type b and meningococci.

Splenic diseases include splenomegaly, where the spleen is enlarged for various reasons. On the other hand, a lack of normal spleen function is called asplenia.

Isolated congenital asplenia (ICAS) is a rare disease in humans that can cause life-threatening bacterial infections in children due to primary immunodeficiency. The infections can include pneumococal sepsis and meningitis.

ICAS is a ribosomopathy, due to autosomal dominant mutation of the "RPSA" gene on chromosome 3p21. Unlike heterotaxy syndrome, the absent spleen is not associated with other structural developmental defects.

An overwhelming post-splenectomy infection (OPSI) or Overwhelming post-splenectomy sepsis (OPSS) is a rare but rapidly fatal infection occurring in individuals following removal of the spleen. The infections are typically characterized by either meningitis or sepsis, and are caused by encapsulated organisms including "Streptococcus pneumoniae".

The risk of OPSI is 0.23–0.42 percent per year, with a lifetime risk of 5 percent. Most infections occur in the first few years following splenectomy, but the risk of OPSI is lifelong. OPSI is almost always fatal without treatment, and modern treatment has decreased the mortality to approximately 40–70 percent. Individuals with OPSI are most commonly treated with antibiotics and supportive care. Measures to prevent OPSI include vaccination and prophylactic antibiotics.

Polysplenia or Chaudhrey's disease is a congenital disease manifested by multiple small accessory spleens, rather than a single, full-sized, normal spleen. Polysplenia sometimes occurs alone, but it is often accompanied by other developmental abnormalities. Conditions associated with polysplenia include gastrointestinal abnormalities, such as intestinal malrotation or biliary atresia, as well as cardiac abnormalities, such as dextrocardia.

There are frequent associated congenital anomalies all related to deviations in the development of anatomical asymmetries in early embryonic stages. These conditions considered together are called "polysplenia syndrome".

Associated conditions include heterotaxy syndrome, intestinal malrotation, situs inversus, biliary atresia, and several cardiac malformations. Associated cardiac conditions include dextrocardia, atrial situs ambiguus, ventricular inversion, and VA concordance with left posterior aorta.

Although present, the multiple small spleens are often ineffective; this is termed functional asplenia.

Increased platelet counts can be due to a number of disease processes:

- Essential (primary)

- Essential thrombocytosis (a form of myeloproliferative disease)

- Other myeloproliferative disorders such as chronic myelogenous leukemia, polycythemia vera, myelofibrosis

- Reactive (secondary)

- Inflammation

- Surgery (which leads to an inflammatory state)

- Hyposplenism (decreased breakdown due to decreased function of the spleen)

- Splenectomy

- Asplenia (absence of normal spleen function)

- Iron deficiency anemia or hemorrhage

Over-medication with drugs that treat thrombocytopenia, such as eltrombopag or romiplostim, may also result in thrombocytosis.

Other causes include the following

- Kawasaki disease

- Soft tissue sarcoma

- Osteosarcoma

- Dermatitis (rarely)

- Inflammatory bowel disease

- Rheumatoid arthritis

- Nephritis

- Nephrotic syndrome

- Bacterial diseases, including pneumonia, sepsis, meningitis, urinary tract infections, and septic arthritis.

The vast majority of causes of thrombocytosis are acquired disorders, but in a few cases, they may be congenital, such as thrombocytosis due to congenital asplenia.

The spleen contains many macrophages (part of the reticuloendothelial system), which are immune cells that phagocytose (eat) and destroy bacteria. In particular, these macrophages are activated when bacteria are bound by IgG antibodies (IgG1 or IgG3) or the complement component C3b. These types of antibodies and complement are immune substances called opsonizers, molecules that bind to the surface of bacteria to facilitate phagocytosis.

When the spleen is no longer present (asplenia), IgG and C3b are still bound to bacteria, but they cannot be removed from the blood circulation due to the loss of the splenic macrophages. Hence the bacteria are free to cause infection.

Patients without spleens often need immunizations against pathogens that normally require opsonization and phagocytosis by macrophages in the spleen. These include common human pathogens with bacterial capsules ("Streptococcus pneumoniae, Salmonella typhi, Neisseria meningitidis, E. coli, Hemophilus influenzae, Streptococcus agalactiae, Klebsiella pneumoniae"). Capsules made of polysaccharides (sugars) permit bacteria to evade phagocytosis by macrophages alone, since only proteins are directly recognized by macrophages in phagocytosis. So humoral immunity in forms of IgG and complement proteins is the human immune system's response against bacterial capsules.

High platelet levels do not necessarily signal any clinical problems, and are picked up on a routine full blood count. However, it is important that a full medical history be elicited to ensure that the increased platelet count is not due to a secondary process. Often, it occurs in tandem with an inflammatory disease, as the principal stimulants of platelet production (e.g. thrombopoietin) are elevated in these clinical states as part of the acute phase reaction.

High platelet counts can occur in patients with polycythemia vera (high red blood cell counts), and is an additional risk factor for complications.

A very small segment of patients report symptoms of erythromelalgia, a burning sensation and redness of the extremities that resolves with cooling and/or aspirin use.

Scientific literature sometimes excludes thrombocytosis from the scope of thrombophilia by definition, but practically, by the definition of thrombophilia as an increased predisposition to thrombosis, thrombocytosis (especially primary thrombocytosis) is a potential cause of thrombophilia. Conversely, secondary thrombocytosis very rarely causes thrombotic complications.

Asplenia with cardiovascular anomalies, also known as Ivemark syndrome and right atrial isomerism, is an example of a heterotaxy syndrome. These uncommon congenital disorders are characterized by defects in the heart, spleen and paired organs such as the lungs and kidneys. Another name is "asplenia-cardiovascular defect-heterotaxy".

Right atrial isomerism is named for its discoverer, Swedish pathologist Biörn Ivemark.

The management of an acute event of vaso-occlusive crisis is the use of potent analgesics (opioids), rehydration with normal saline or Ringer's lactate, treatment of malaria (whether symptomatic or not) using artemisinin combination therapy, and the use of oxygen via face mask, especially for acute chest syndrome. Hyperbaric oxygen has also been shown to be a useful adjunct in pain reduction. Antibiotics may be utilized because patients usually have occult infection due to a "functional asplenia".

Purpura fulminans is rare and most commonly occurs in babies and small children but can also be a rare manifestation in adults when it is associated with severe infections. For example, Meningococcal septicaemia is complicated by purpura fulminans in 10–20% of cases among children. Purpura fulminans associated with congenital (inherited) protein C deficiency occurs in 1:500,000–1,000,000 live births.

Persons with component deficiencies in the final common complement pathway (C3,C5-C9) are more susceptible to "N. meningitidis" infection than complement-satisfactory persons, and it was estimated that the risk of infection is 7000 times higher in such individuals. In addition, complement component-deficient populations frequently experience frequent meningococcal disease since their immune response to natural infection may be less complete than that of complement non-deficient persons.

Inherited properdin deficiency also is related, with an increased risk of contracting meningococcal disease. Persons with functional or anatomic asplenia may not efficiently clear encapsulated "Neisseria meningitidis" from the bloodstream Persons with other conditions associated with immunosuppression also may be at increased risk of developing meningococcal disease.

A vaso-occlusive crisis is a common painful complication of sickle cell anemia in adolescents and adults. It is a form of sickle cell crisis. Sickle cell anemia – most common in those of African, Hispanic, and Mediterranean origin – leads to sickle cell crisis when the circulation of blood vessels is obstructed by sickled red blood cells, causing ischemic injuries. The most common complaint is of pain, and recurrent episodes may cause irreversible organ damage. One of the most severe forms is the acute chest syndrome which occurs as a result of infarction of the lung parenchyma. This can rapidly result in death. Other types of vaso-occlusive crisis in sickle cell anemia include dactylitis, priapism, abdominal pain, and jaundice.

A 1998 review noted that life expectancy is usually normal, but that there have occasionally been reported neonatal deaths due to PCD. A 2016 longitudinal study followed 151 adults with PCD for a median of 7 years. Within that span, 7 persons died with a median age of 65.

Although its cause is poorly understood, situs ambiguous has been linked to family history of malformations and maternal cocaine use, suggesting both genetic and environmental factors play a role. Several genes in the TGF-beta pathway, which controls left-right patterning of viseral organs across the body axis, have been indicated in sporadic and familial cases of atrial isomerism.

There does not appear to be a screening method for prevention of heterotaxy syndrome. However, genetic testing in family members that display atrial isomerism or other cardiac malformations may help to discern risk for additional family members, especially in X-linked causes of heterotaxy syndrome.

The cause of heterotaxy is unknown.

The Ivemark Syndrome Association, which is based in Dorset,

is one of the organisations dedicated to helping sufferrers and funding research.

The term leukemoid reaction describes an increased

white blood cell count, or leukocytosis, which is a physiological response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). It often describes the presence of immature cells such as myeloblasts or red blood cells with nuclei in the peripheral blood.

It may be lymphoid or myeloid.

As noted above, a leukemoid reaction is typically a response to an underlying medical issue. Causes of leukemoid reactions include:

- Severe hemorrhage (retroperitoneal hemorrhage)

- Drugs

- Use of sulfa drugs

- Use of dapsone

- Use of glucocorticoids

- Use of G-CSF or related growth factors

- All-trans retinoic acid (ATRA)

- Ethylene glycol intoxication

- Infections

- Clostridium difficile

- Tuberculosis

- Pertussis

- Infectious mononucleosis (lymphocyte predominant)

- Visceral larva migrans (eosinophil predominant)

- Asplenia

- Diabetic ketoacidosis

- Organ necrosis

- Hepatic necrosis

- Ischemic colitis

- As a feature of trisomy 21 in infancy (incidence of ~10%)

- As a paraneoplastic phenomenon (rare)

Because the risk of meningococcal disease is increased among USA's military recruits, all military recruits routinely receive primary immunization against the disease.

There have been vast amounts of research on the clinical features, racial disparities, and physiological mechanisms of heterotaxy syndrome dating back to 1973.

Mishra et al. published a review in November 2015 describing current knowledge of cardiac and non-cardiac abnormalities associated with situs ambiguous. The author stresses the importance of genetic testing prior to deciding a prognosis for affected patients. She also proposes prenatal screening and evaluation in cases at risk for development of situs ambiguous.

Recent studies have shown higher rates of heterotaxy syndrome among Hispanic infants of Mexican descent, as well as female infants of non-Hispanic black and white mothers. Additional studies must be done to clarify the mechanisms behind racial disparities in heterotaxy syndrome. Individuals of Asian descent show a higher prevalence of heterotaxy syndrome in general than members of the Western world.

The National Birth Defects Prevention study (October 2014) attempted to link clinical presentations of situs ambiguous to demographics in an epidemiological study. This proved a difficult task due to the vast differences in presentation of this disorder. However, the authors are hopeful that finding a link can help inform clinical decision-making, predictive analyses, and future outcomes.