RAO may arise typically due to endothelial injury and decreased blood flow during the insertion of sheaths and catheters at the catheterization site, as well as during manipulations throughout the procedure. More specifically, during sheath insertion, the intima of the vessel may be damaged, leading to local exposure of collagen fibers and tissue factors, while blood flow is halted in the radial artery. Consequently, the coagulation cascade is triggered, causing platelets and fibrin to aggregate at the site of vascular injury, leading to thrombus formation and local thrombosis of the radial artery.

However, arterial occlusion following percutaneous coronary procedures could be a result of compression phenomena, due to local induction by the catheterization process edema or hematoma ^[1][2][12,13].

The dual blood supply to the hand confers a quiescent character of RAO in most patients, which results in the majority of cases going undetected. Symptoms indicating RAO, such as pain at the site of the thrombosis, paresthesia, and decreased limb function, are only present in a minority of cases, accounting for approximately 0.2% of patients. Hand ischemia due to RAO occurs exclusively in individuals with insufficient collateral circulation, mostly on account of anatomic variations ^[3][14].

Doppler ultrasonography is widely considered to be the gold standard method for assessing radial artery patency following transradial access, owing to its ability to provide both hemodynamic information and anatomical details of the vessel. Nevertheless, current research has investigated alternative methods, taking into account factors such as cost, time, and availability, in order to assess their efficacy in detecting RAO.

Digital plethysmography, using a modified reverse Barbeau’s test, is a more affordable and less time-consuming method compared to a Doppler ultrasound. Plethysmography sampling involves placing a digital sensor on the index finger or thumb to evaluate the patency of the radial artery after transradial access. This is achieved by compressing both the radial and ulnar arteries, causing the oximetry signal to be lost. The release of the radial artery leads to the recovery of the signal, indicating radial artery patency.

While the modified reverse Barbeau’s test, similar to the modified Allen’s test, has been, until now, used as a method to clinically assess the adequacy of the ulnar artery’s collateral flow before the radial artery’s catheterization, in recent randomized controlled trials (RCTs), the effectiveness of this method has been compared to that of Doppler ultrasonography (USG) in detecting RAO. Important findings indicate that there is no significant difference in the efficacy of the two methods ^[3][4][5][14,15,16].

Laser perfusion imaging (LPI) has recently emerged as a novel and operator-independent diagnostic tool to evaluate radial artery perfusion following transradial catheterization. This diagnostic method involves capturing a color-coded perfusion image of the hand palm in a state of rest. Subsequently, a second image is captured after occluding the ulnar artery with pressure. The diagnosis of RAO is determined by calculating the radial perfusion index (RPI), which is the ratio between the basal radial perfusion and the value measured under ulnar occlusion. Notably, LPI is particularly useful for patients with anatomical variations presenting difficulties during catheterization. Furthermore, the lack of direct skin contact during LPI eliminates any pain or infection associated with probe contact. Additionally, the operator-independent nature of LPI makes it more objective and cost-effective than other methods. Although LPI is a relatively new technology, its potential as a reliable and practical diagnostic tool for RAO warrants further investigation ^[6][17].

Many factors contribute mainly to thrombus formation and, consequently, predisposition to RAO. These can be divided into modifiable and non-modifiable, or patient-related and procedurally-induced risk factors.

Several patient-related risk factors have been identified for RAO, including younger age, female sex, low body mass index, diabetes mellitus, dyslipidemia, peripheral artery disease, multiple vessel coronary artery disease, reduced renal function, and previous radial artery cannulation. Among these factors, cardiovascular risk factors could be modified over the years through lifestyle changes and pharmacological interventions, whereas previous radial artery cannulation is an unmodifiable risk factor that does not constitute a generic characteristic. Unfortunately, repeated radial cannulation leads to intimal hyperplasia and intima-media thickening, resulting in reduced lumen diameter ^[7][18].

On the other hand, hypertension has been proposed to exert a protective effect against RAO, by inducing a hyperdynamic state within the arterial lumen, leading to gradual reopening of the occluded portion of the artery. Consequently, unlike other known risk factors for atherosclerosis, hypertension appears to have a unique effect in this regard ^[8][19].

On top of that, there are some procedural RAO inducing factors, which could be mitigated by the operator’s experience and focus during the operation on minimizing traumatic injury to the radial artery. These risk factors include a sheath-to-artery ratio greater than 1, repeated unsuccessful attempts at a radial artery puncture, a radial artery spasm, the use of multiple catheters, periprocedural anticoagulation, occlusive hemostasis and, finally, longer periprocedural and hemostasis times.

Post-procedural pain at the cannulation site and hematoma formation are both considered to be contributing factors to thrombotic radial artery occlusion. Paradoxically, the formation of a hematoma after removal of the hemostatic device is thought to increase the risk of thrombus formation, as the operator may need to manipulate the access site in order to minimize its extent ^[7][9][18,20].

The minimization of the modifiable risk factors could be a helpful tool for reducing rates of post-procedural radial artery thrombosis ^[10][6].

A recurrent endothelial injury from repeated punctures can lead to damage of the vessel wall and early thrombus formation. Thus, the pre-interventional visualization of the radial artery in both limbs using Doppler ultrasonography is suggested in order to assess the radial artery’s characteristics. More specifically, it is useful for the selection of an artery with a wider diameter, and the illustration of the caliber and depth of the vessel. As a result, the cannulation of the artery is more easily achieved, and the need for repeated puncture attempts is reduced ^[11][12][28,29]. Additionally, this imaging modality can aid in selecting an appropriate sheath size to reduce the sheath-to-artery mismatch, thereby minimizing the risk of RAO ^[13][3].

Minimizing the size of equipment used in coronary interventions is crucial in reducing the incidence of RAO. A sheath-to-artery diameter ratio mismatch can result in an injury to the radial artery wall, endothelial dysfunction, blood flow disturbance, and chronic vascular remodeling. Studies have shown that a sheath-to-artery diameter ratio of less than 1 is associated with a lower risk of RAO.

It is argued that the subcutaneous injection of nitroglycerin at the radial artery puncture site offers significant vasodilation of the radial artery. This approach facilitates the cannulation. As a result, the number of punctures and the incidence of radial artery spasm are reduced ^[14][15][16][37,38,39].

Even so, its impact on radial artery occlusion is controversial. Until recently, the pre-hemostasis injection of 500 μg nitroglycerin seemed to reduce the rate of RAO due to the influence of nitrous oxide on the intimal inflammation and hyperplasia of the radial artery ^[14][17][27,37]. However, a recently published study came to overthrow this argument by showing that nitroglycerin had no impact on the incidence of RAO regardless of its administration timing, whether upon sheath insertion or before its removal ^[13][3].

Adequate anticoagulation is an important aspect within the multifactorial preventive strategy for the prevention of RAO, as its pathogenesis is majorly associated with thrombus formation. A bolus dose of 50 IU/Kg or 5000 IU unfractionated heparin (UFH) was, until recently, recommended to be efficient in RAO prevention, regardless of the delivery route, whether intravenously or via the arterial sheath ^[18][42]. For this reason, the effect of the standard heparinization dose on RAO has been compared with higher or lower doses in multiple RCTs.

The procedure between sheath removal and the removal of the hemostatic device is defined as hemostasis. Occlusive hemostasis, hemostatic devices, and hemostasis duration play a major role in thrombus formation, due to the initiation of decreased blood flow.

Evidence-based contemporary protocols have shown that not only has the option for different hemostatic devices little effect on radial artery thrombosis, but also that the presence of non-occlusive hemostasis appears to be a much more important factor ^[19][20][21][47,48,49].

5. RAO Treatment

Although RAO is suggested to be treated only in symptomatic patients, a patent radial artery is of great importance, because otherwise it could not be used for coronary artery catheterization in the future, for grafting purposes during coronary artery bypass surgeries, and for arteriovenous fistula formation in case of hemodialysis. In addition, prior RAO is a contraindication for the ipsilateral transulnar approach, which further limits the operator’s options in the catheterization laboratory, especially when time is of the essence. If RAO is diagnosed before discharge, the ipsilateral compression of the ulnar artery for an hour may be an effective technique in order to regain the artery’s patency. This method is associated with an increase in radial blood flow, thereby initiating the release of vasodilator mediators ^[22][67]. Apart from this, for patients with persistent RAO, the therapeutic options include either medical treatment with anticoagulation agents for 1–3 months, or percutaneous retrograde revascularization ^{[23][24][25][26]}[68,69,70,71]. In most cases, the anticoagulation therapy of choice for people suffering from symptomatic RAO is a body-weight-adjusted dosage of low-molecular-weight-heparin (LMWH) agents. More specifically, in the majority of patients it is either enoxaparin 10 mg per 10 kg body weight, subcutaneously (s.c.) twice daily administered or, for people weighting between 50–100 kg, s.c. fondaparinux 7.5 mg is administered once daily. Prophylactic doses of 40 mg or 2.5 mg once daily of enoxaparin or fondaparinux, respectively are only used in patients, who are simultaneously treated with dual antiplatelet therapy due to coronary artery disease ^[27][28][72,73]. In addition to that, the use of novel oral anticoagulation agents and, especially, apixaban has been recently proposed as an alternative and more convenient option to subcutaneous therapy. Nevertheless, its benefit should be further investigated, because the current literature is limited ^[29][74]. The restoration of the blood flow of the radial artery can be also interventionally achieved from a proximal part of the forearm, where the pulse is still palpated. In patients in whom the insertion of a 5F sheath and a guide wire is successful, a small channel could be opened and, therefore, depicted with the introduction of contrast medium. More severe and total occlusive lesions could be over-passed with the help of a J-typed guidewire and, when this method fails, the thrombi from the radial artery may be aspirated via a balloon dilation and drilling technique ^[23][68]. Of note, retrograde recanalization can be also pursued in our era through dTRA. The most popular method that has been proposed lately is the aspiration of the thrombus directly through the inducer sheath, or through an aspiration catheter. Furthermore, promising results have been retrieved by the conduct of balloon angioplasty through the dTRA, or the transcatheter administration of thrombolytic therapy ^[30][31][64,75]. These techniques are considered safe for major events and vascular complications, as only minimal hematomas (EASY Class I-II) and one case of artery perforation have been described. Finally, the retrograde reopening of the radial artery offers a long term patency result—after one, three, six and nine months from the intervention—in most of the investigated cohorts ^[32][76]. Nonetheless, these invasive management strategies to restore blood flow cannot be routinely utilized, and the use of this recanalized radial artery as a graft for coronary bypass surgery or for arteriovenous fistula formation could be a risky choice, as this subject is not sufficiently investigated.